owencqueen/cgbench_data huggingface dataset:
Gene: DICER1 (HGNC:17098)
Evidence Code: PM1 — Moderate
Modification Type: Disease-specific
Residues affecting metal ion-binding: codons p.S1344, p.E1705, p.D1709, p.D1713, p.G1809, p.D1810, p.E1813
Gene: DICER1 (HGNC:17098)
Evidence Code: PM1 — Supporting
Modification Type: Strength
Residues in the RNase IIIb domain (p.Y1682 – p.S1846),
besides the metal ion-binding residues (see PM1).
Gene: DICER1 (HGNC:17098)
Evidence Code: PM5 — Moderate
Modification Type: General recommendation
Missense variant under evaluation should have equal or worse Grantham score. Splicing should be
ruled out with either RNA data or agreement in splicing predictors (MaxEntScan and SpliceAI) that show no splicing effects (either an increase in the canonical
splice site score or a decrease in the canonical splice site score by no more than 10% AND no putative cryptic splice sites are created).
The other variant must be interpreted as pathogenic by the ClinGen DICER1 VCEP. Likely pathogenic changes do not apply. This rule cannot be applied in combination with
PM1 or PS1.
Gene: DICER1 (HGNC:17098)
Evidence Code: PP3 — Supporting
Modification Type: Disease-specific
For missense variants, REVEL score ≥ 0.75 OR agreement in splicing predictors predict splicing effects. For splicing variants, concordance of MaxEntScan and SpliceAI.
PP3 may be applied for intronic variants located in reference to exons at +3 to +5 for donor splice sites or -3 to -5 for acceptor splice sites (PMID: 27313609) and have a predicted decrease in the score of the canonical splice site by at least 75%, regardless of the predicted creation or presence of a putative cryptic splice site. Must have concordance of both MaxEntScan and SpliceAI.
Gene: DICER1 (HGNC:17098)
Evidence Code: BP4 — Supporting
Modification Type: Disease-specific
For missense variants, REVEL score < 0.50 and agreement in splicing predictors that no splicing effects are predicted. For synonymous/intronic/non-coding variants concordance of MaxEntScan and SpliceAI.
MaxEntScan and SpliceAI should predict either no change in splicing, an increase in canonical splice site score, or a decrease of the canonical splice site score by no more than 10% AND no putative cryptic splice sites are created.
Gene: DICER1 (HGNC:17098)
Evidence Code: BP7 — Supporting
Silent variant
OR Intronic variant at or beyond +7 to -21 positions
OR Other intronic or non-coding variant if the variant is the reference nucleotide in ≥1 primate and/or ≥4 mammalian species.
Caveat: Variant must meet BP4 to apply BP7