owencqueen/cgbench_data huggingface dataset:
Gene: TECTA (HGNC:11720)
Evidence Code: PVS1 — Original ACMG Summary
Null variant (nonsense, frameshift, canonical +/−1 or 2 splice sites, initiation codon, single or multi-exon deletion) in a gene where loss of function (LOF) is a known mechanism of disease.
Caveats:
 • Beware of genes where LOF is not a known disease mechanism (e.g. GFAP, MYH7).
 • Use caution interpreting LOF variants at the extreme 3’ end of a gene.
 • Use caution with splice variants that are predicted to lead to exon skipping but leave the remainder of the protein intact.
 • Use caution in the presence of multiple transcripts.
Gene: TECTA (HGNC:11720)
Evidence Code: PVS1 — Very Strong
Null variant in a gene with established LOF as a disease mechanism; see PVS1_Strong, PVS1_Moderate, PVS1_Supporting for reduced evidence applications.
Gene: TECTA (HGNC:11720)
Evidence Code: PVS1 — Strong
See PVS1 flow chart for PVS1_Strong variants in gene where LOF is a known mechanism of disease.
Gene: TECTA (HGNC:11720)
Evidence Code: PVS1 — Moderate
See PVS1 flowchart for PVS1_Moderate variants in gene where LOF is a known mechanism of disease.
Gene: TECTA (HGNC:11720)
Evidence Code: PVS1 — Supporting
See PVS1 flowchart for PVS1_Supporting variants in gene where LOF is a known mechanism of disease.
Gene: TECTA (HGNC:11720)
Evidence Code: PS1 — Original ACMG Summary
Same amino acid change as a previously established pathogenic variant regardless of nucleotide change.
Example: Val->Leu caused by either G>C or G>T in the same codon.
Caveat: Beware of changes that impact splicing rather than at the amino acid/protein level.
Gene: TECTA (HGNC:11720)
Evidence Code: PS1 — Strong
Same amino acid change as an established pathogenic variant; OR
splice variants at same nucleotide and with similar impact prediction as previously reported pathogenic variant.
Gene: TECTA (HGNC:11720)
Evidence Code: PS2 — Original ACMG Summary
De novo (both maternity and paternity confirmed) in a patient with the disease and no family history.
Note: Confirmation of paternity only is insufficient. Egg donation, surrogate motherhood, errors in embryo transfer, etc. can contribute to non-maternity.
Gene: TECTA (HGNC:11720)
Evidence Code: PS2 — Very Strong
4 points per tables 5a and 5b:
Examples: 2 proven de novo occurrences; OR 1 proven + 2 assumed de novo occurrences; OR 4 assumed de novo occurrences.
Gene: TECTA (HGNC:11720)
Evidence Code: PS2 — Strong
2 points per tables 5a and 5b:
Examples: 1 proven de novo occurrence; OR 2 assumed de novo occurrences.
Gene: TECTA (HGNC:11720)
Evidence Code: PS2 — Moderate
1 point per tables 5a and 5b:
Examples: 1 proven de novo occurrence (phenotype consistent but not specific to gene); OR 1 assumed de novo occurrence; OR 2 assumed de novo occurrences (phenotype/gene not specific).
Gene: TECTA (HGNC:11720)
Evidence Code: PS2 — Supporting
0.5 points per tables 5a and 5b:
Example: 1 assumed de novo occurrence (phenotype/gene not specific).
Gene: TECTA (HGNC:11720)
Evidence Code: PS3 — Original ACMG Summary
Well-established in vitro or in vivo functional studies supportive of a damaging effect on the gene or gene product.
Note: Functional studies that have been validated and shown to be reproducible and robust in a clinical diagnostic laboratory setting are considered the most well-established.
Gene: TECTA (HGNC:11720)
Evidence Code: PS3 — Strong
Knock-in mouse model demonstrates the phenotype.
Gene: TECTA (HGNC:11720)
Evidence Code: PS3 — Moderate
Validated functional studies show a deleterious effect (predefined list).
Gene: TECTA (HGNC:11720)
Evidence Code: PS3 — Supporting
Functional studies with limited validation show a deleterious effect.
Gene: TECTA (HGNC:11720)
Evidence Code: PS4 — Original ACMG Summary
The prevalence of the variant in affected individuals is significantly increased compared to the prevalence in controls.
Note 1: Relative risk (RR) or odds ratio (OR), as obtained from case-control studies, is >5.0 and the confidence interval around the estimate of RR or OR does not include 1.0. See manuscript for detailed guidance.
Note 2: In instances of very rare variants where case-control studies may not reach statistical significance, the prior observation of the variant in multiple unrelated patients with the same phenotype, and its absence in controls, may be used as moderate level of evidence.
Gene: TECTA (HGNC:11720)
Evidence Code: PS4 — Strong
Fisher Exact or Chi-Squared analysis shows statistical increase in cases over controls, OR Autosomal dominant: ≥15 probands with variant, and variant meets PM2.
Gene: TECTA (HGNC:11720)
Evidence Code: PS4 — Moderate
Autosomal dominant: ≥6 probands with variant, and variant meets PM2.
Gene: TECTA (HGNC:11720)
Evidence Code: PS4 — Supporting
Autosomal dominant: ≥2 probands with variant, and variant meets PM2.
Gene: TECTA (HGNC:11720)
Evidence Code: PM1 — Original ACMG Summary
Located in a mutational hot spot and/or critical and well-established functional domain (e.g. active site of an enzyme) without benign variation.
Gene: TECTA (HGNC:11720)
Evidence Code: PM1 — Moderate
Mutational hot spot or well-studied functional domain without benign variation (KCNQ4 pore-forming region; Gly residues in Gly-X-Y motifs of COL11A2, COL4A3, COL4A4, and COL4A5).
Gene: TECTA (HGNC:11720)
Evidence Code: PM2 — Original ACMG Summary
Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes or Exome Aggregation Consortium.
Caveat: Population data for indels may be poorly called by next generation sequencing.
Gene: TECTA (HGNC:11720)
Evidence Code: PM2 — Moderate
Absent/Rare in population databases (absent or ≤0.00007 (0.007%) for autosomal recessive, ≤0.00002 (0.002%) for autosomal dominant).
Gene: TECTA (HGNC:11720)
Evidence Code: PM2 — Supporting
Low MAF in population databases <0.0007 (0.07%) for autosomal recessive.
Gene: TECTA (HGNC:11720)
Evidence Code: PM3 — Original ACMG Summary
For recessive disorders, detected in trans with a pathogenic variant
Note: This requires testing of parents (or offspring) to determine phase.
Gene: TECTA (HGNC:11720)
Evidence Code: PM3 — Very Strong
4 points awarded from tables 7a and 7b:
Example: Detected in trans in ≥4 probands with a pathogenic variant (recessive).
Gene: TECTA (HGNC:11720)
Evidence Code: PM3 — Strong
2 points awarded from tables 7a and 7b:
Example: Detected in trans in 2 probands with a pathogenic variant (recessive).
Gene: TECTA (HGNC:11720)
Evidence Code: PM3 — Moderate
1 point awarded from tables 7a and 7b:
Example: Detected in trans with a pathogenic variant (recessive).
Gene: TECTA (HGNC:11720)
Evidence Code: PM3 — Supporting
0.5 points awarded from tables 7a and 7b:
Examples: Two variants that meet PM2_Supporting detected in trans; OR a homozygous variant meeting PM2_Supporting.
Gene: TECTA (HGNC:11720)
Evidence Code: PM4 — Original ACMG Summary
Protein length changes due to in-frame deletions/insertions in a non-repeat region or stop-loss variants.
Gene: TECTA (HGNC:11720)
Evidence Code: PM4 — Moderate
Protein length change due to an in-frame deletion or insertion that are not located in repetitive regions.
Gene: TECTA (HGNC:11720)
Evidence Code: PM5 — Original ACMG Summary
Novel missense change at an amino acid residue where a different missense change determined to be pathogenic has been seen before.
Example: Arg156His is pathogenic; now you observe Arg156Cys.
Caveat: Beware of changes that impact splicing rather than at the amino acid/protein level.
Gene: TECTA (HGNC:11720)
Evidence Code: PM5 — Strong
Missense change at same codon as two different pathogenic missense variants.
Gene: TECTA (HGNC:11720)
Evidence Code: PM5 — Moderate
Missense change at same codon as another pathogenic missense variant.
Gene: TECTA (HGNC:11720)
Evidence Code: PM6 — Original ACMG Summary
Assumed de novo, but without confirmation of paternity and maternity.
Gene: TECTA (HGNC:11720)
Evidence Code: PM6 — Moderate
See PS2 above.
Gene: TECTA (HGNC:11720)
Evidence Code: PP1 — Original ACMG Summary
Co-segregation with disease in multiple affected family members in a gene definitively known to cause the disease.
Note: May be used as stronger evidence with increasing segregation data.
Gene: TECTA (HGNC:11720)
Evidence Code: PP1 — Strong
Segregation in three affected relatives for recessive and five affected relatives for dominant.
Gene: TECTA (HGNC:11720)
Evidence Code: PP1 — Moderate
Segregation in two affected relatives for recessive and four affected relatives for dominant.
Gene: TECTA (HGNC:11720)
Evidence Code: PP1 — Supporting
Segregation in one affected relative for recessive and two affected relatives for dominant.
Gene: TECTA (HGNC:11720)
Evidence Code: PP2 — Original ACMG Summary
Missense variant in a gene that has a low rate of benign missense variation and where missense variants are a common mechanism of disease.
Gene: TECTA (HGNC:11720)
Evidence Code: PP3 — Original ACMG Summary
Multiple lines of computational evidence support a deleterious effect on the gene or gene product (conservation, evolutionary, splicing impact, etc.).
Caveat: As many in silico algorithms use the same or very similar input for their predictions, each algorithm should not be counted as an independent criterion. PP3 can be used only once in any evaluation of a variant.
Gene: TECTA (HGNC:11720)
Evidence Code: PP3 — Supporting
REVEL score ≥0.7, or predicted impact to splicing using MaxEntScan.
Gene: TECTA (HGNC:11720)
Evidence Code: PP4 — Original ACMG Summary
Patient’s phenotype or family history is highly specific for a disease with a single genetic etiology.
Gene: TECTA (HGNC:11720)
Evidence Code: PP4 — Supporting
Patient's phenotype highly specific for gene or fully sequenced gene set (see specifications in Table 7).
Gene: TECTA (HGNC:11720)
Evidence Code: PP5 — Original ACMG Summary
Reputable source recently reports variant as pathogenic, but the evidence is not available to the laboratory to perform an independent evaluation.
Gene: TECTA (HGNC:11720)
Evidence Code: BA1 — Original ACMG Summary
Allele frequency is above 5% in Exome Sequencing Project, 1000 Genomes or Exome Aggregation Consortium.
Gene: TECTA (HGNC:11720)
Evidence Code: BA1 — Stand Alone
MAF of ≥0.005 (0.5%) for autosomal recessive; MAF of ≥0.001 (0.1%) for autosomal dominant.
Gene: TECTA (HGNC:11720)
Evidence Code: BS1 — Original ACMG Summary
Allele frequency is greater than expected for disorder.
Gene: TECTA (HGNC:11720)
Evidence Code: BS1 — Strong
MAF of ≥0.003 (0.3%) for autosomal recessive; MAF of ≥0.0002 (0.02%) for autosomal dominant. Likely benign, provided there is no conflicting evidence.
Gene: TECTA (HGNC:11720)
Evidence Code: BS1 — Supporting
MAF of ≥0.0007 (0.07%) for autosomal recessive. No BS1_Supporting criteria for autosomal dominant.
Gene: TECTA (HGNC:11720)
Evidence Code: BS2 — Original ACMG Summary
Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age.
Gene: TECTA (HGNC:11720)
Evidence Code: BS2 — Strong
Observation of variant (biallelic with known pathogenic variant for recessive) in controls inconsistent with disease penetrance.
Gene: TECTA (HGNC:11720)
Evidence Code: BS3 — Original ACMG Summary
Well-established in vitro or in vivo functional studies show no damaging effect on protein function or splicing.
Gene: TECTA (HGNC:11720)
Evidence Code: BS3 — Supporting
Functional study shows no deleterious effect (predefined list).
Gene: TECTA (HGNC:11720)
Evidence Code: BS4 — Original ACMG Summary
Lack of segregation in affected members of a family.
Caveat: The presence of phenocopies for common phenotypes (i.e. cancer, epilepsy) can mimic lack of segregation among affected individuals. Also, families may have more than one pathogenic variant contributing to an autosomal dominant disorder, further confounding an apparent lack of segregation.
Gene: TECTA (HGNC:11720)
Evidence Code: BS4 — Strong
Non-segregation with disease.
Gene: TECTA (HGNC:11720)
Evidence Code: BP1 — Original ACMG Summary
Missense variant in a gene for which primarily truncating variants are known to cause disease.
Gene: TECTA (HGNC:11720)
Evidence Code: BP2 — Original ACMG Summary
Observed in trans with a pathogenic variant for a fully penetrant dominant gene/disorder or observed in cis with a pathogenic variant in any inheritance pattern.
Gene: TECTA (HGNC:11720)
Evidence Code: BP2 — Supporting
Observed in trans with a dominant variant/observed in cis with a pathogenic variant (use with caution).
Gene: TECTA (HGNC:11720)
Evidence Code: BP3 — Original ACMG Summary
In frame-deletions/insertions in a repetitive region without a known function.
Gene: TECTA (HGNC:11720)
Evidence Code: BP3 — Supporting
In-frame indels in repeat region without known function.
Gene: TECTA (HGNC:11720)
Evidence Code: BP4 — Original ACMG Summary
Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc)
Caveat: As many in silico algorithms use the same or very similar input for their predictions, each algorithm cannot be counted as an independent criterion. BP4 can be used only once in any evaluation of a variant.
Gene: TECTA (HGNC:11720)
Evidence Code: BP4 — Supporting
Computational evidence suggests no impact; REVEL score ≤0.15 or no impact to splicing in MaxEntScan.
Gene: TECTA (HGNC:11720)
Evidence Code: BP5 — Original ACMG Summary
Variant found in a case with an alternate molecular basis for disease.
Gene: TECTA (HGNC:11720)
Evidence Code: BP5 — Supporting
Variant in an autosomal dominant gene found in a patient with an alternate explanation.
Gene: TECTA (HGNC:11720)
Evidence Code: BP6 — Original ACMG Summary
Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation.
Gene: TECTA (HGNC:11720)
Evidence Code: BP7 — Original ACMG Summary
A synonymous variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved.
Gene: TECTA (HGNC:11720)
Evidence Code: BP7 — Supporting
Silent variant with no predicted impact to splicing.