ClinVar Miner

Submissions for variant NM_001754.5(RUNX1):c.314A>C (p.His105Pro)

dbSNP: rs1569084116
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Myeloid Malignancy Variant Curation Expert Panel RCV000824707 SCV000965659 likely pathogenic Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 2019-07-26 reviewed by expert panel curation The NM_001754.4:c.314A>C (p.His105Pro) variant affects one of the residues (AA 105-204) within the RHD (PM1_Supporting). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2). This missense variant has a REVEL score >0.75 (0.953) (PP3). This variant is a missense change at the same residue (p.His105Pro) where a different missense change has been previously established as a likely pathogenic variant (NM_001754.4:c.315C>A (p.His105Glu)) based on MM-VCEP rules for RUNX1 and RNA data or agreement in splicing predictors (SSF and MES) show no splicing effects (PM5_Supporting). This variant has been reported in one proband meeting at least one of the RUNX1-phenotypic criteria (PS4_ Supporting; SCV000807773.1). In summary, this variant meets criteria to be classified as likely pathogenic. ACMG/AMP criteria applied, as specified by the ClinGen Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PM2, PP3, PM1_supporting, PM5_supporting, PS4_supporting.
PreventionGenetics, part of Exact Sciences RCV003389725 SCV000807773 uncertain significance RUNX1-related disorder 2024-01-04 no assertion criteria provided clinical testing The RUNX1 c.314A>C variant is predicted to result in the amino acid substitution p.His105Pro. To our knowledge, this variant has not been reported in RUNX1-related patients in the literature or in a large population database, indicating this variant is rare. This variant is interpreted as likely pathogenic by the ClinGen Myeloid Malignancy Variant Curation Expert Panel (https://erepo.clinicalgenome.org/evrepo/ui/interpretation/42a3f999-4991-4180-8cb2-0e8975c5e5bb). Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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