Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • See Evidence submitted by expert panel for details.

Variant: NM_001754.4(RUNX1):c.1160G>C (p.Gly387Ala)

CA410147917

532662 (ClinVar)

Gene: RUNX1
Condition: hereditary thrombocytopenia with normal platelets-hematological cancer predisposition syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 796f47f4-6c31-4833-8a66-03f0dc55514a
Approved on: 2019-07-26
Published on: 2019-08-02

HGVS expressions

NM_001754.4:c.1160G>C
NM_001754.4(RUNX1):c.1160G>C (p.Gly387Ala)
NC_000021.9:g.34792418C>G
CM000683.2:g.34792418C>G
NC_000021.8:g.36164715C>G
CM000683.1:g.36164715C>G
NC_000021.7:g.35086585C>G
NG_011402.2:g.1197294G>C
NM_001001890.2:c.1079G>C
ENST00000300305.7:c.1160G>C
ENST00000344691.8:c.1079G>C
ENST00000399240.5:c.887G>C
ENST00000437180.5:c.1160G>C
ENST00000482318.5:c.*750G>C
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Uncertain Significance

Met criteria codes 2
PS4_Supporting BP4
Not Met criteria codes 16
PS1 PS3 PP1 PP3 PVS1 PM5 PM4 PM1 PM2 PM6 BA1 BS1 BS4 BS3 BP7 BP2

Evidence Links 1

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Myeloid Malignancy VCEP
The NM_001754.4:c.1160G>C (p.Gly387Ala) variant has been reported in one proband meeting at least one of the RUNX1-phenotypic criteria (PS4_ Supporting; PMID: 27210295). This missense variant has a REVEL score <0.15 (0.141) and SSF and MES predict either an increase in the 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 (BP4). The gnomAD Allele Frequency of this variant is 0.00001. In summary, the clinical significance of this variant is uncertain (VUS). ACMG/AMP criteria applied, as specified by the ClinGen Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PS4_ supporting, BP4.
Met criteria codes
PS4_Supporting
1 Proband
Germline variant (46.3%) in 55 yr old male with myeloid neoplasm along with eosinophilia and FGFR1 gene rearrangement and a somatic R201* variant. Brother poor SCT mobilizer with same germline G387A variant, not counted. PubMed:27210295
BP4
REVEL: 0.141 <0.15 and agreement in splicing predictors (SSF and MES) predict no splicing effects.
Not Met criteria codes
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM2
gnomAD Allele Frequency 0.00001
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP7
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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