Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV004736323 | SCV005367740 | uncertain significance | Hereditary thrombocytopenia and hematologic cancer predisposition syndrome | 2024-09-25 | reviewed by expert panel | curation | NM_001754.5(RUNX1):c.1162T>A (p.Ser388Thr) is a missense variant. This variant is completely absent from all population databases with at least 20x coverage for RUNX1 in gnomAD (PM2_supporting). This missense variant has a REVEL score <0.50 (0.154) and a spliceAI score <0.2 (0.0) (BP4). The c.1162T>A variant is the same amino acid change (p.Ser388Thr) as a previously established likely pathogenic variant (ClinVar ID 561222) curated using MM-VCEP rules for RUNX1 and RNA data or agreement in splicing predictors (SSF and MES) show no splicing effects (PS1_Moderate). In summary, the clinical significance of this variant is uncertain. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PM2_supporting, BP4, PS1_moderate. |
Ambry Genetics | RCV003191652 | SCV003877645 | uncertain significance | Inborn genetic diseases | 2023-02-28 | criteria provided, single submitter | clinical testing | The c.1162T>A (p.S388T) alteration is located in exon 9 (coding exon 8) of the RUNX1 gene. This alteration results from a T to A substitution at nucleotide position 1162, causing the serine (S) at amino acid position 388 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |