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]
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  • See Evidence submitted by expert panel for details.

Variant: NM_001754.4(RUNX1):c.367G>C (p.Asp123His)

CA10014524

429813 (ClinVar)

Gene: RUNX1
Condition: hereditary thrombocytopenia with normal platelets-hematological cancer predisposition syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 7e5378c7-f9d9-470d-9323-32fe9a5a69f7
Approved on: 2019-07-29
Published on: 2019-08-02

HGVS expressions

NM_001754.4:c.367G>C
NM_001754.4(RUNX1):c.367G>C (p.Asp123His)
NC_000021.9:g.34880698C>G
CM000683.2:g.34880698C>G
NC_000021.8:g.36252995C>G
CM000683.1:g.36252995C>G
NC_000021.7:g.35174865C>G
NG_011402.2:g.1109014G>C
NM_001001890.2:c.286G>C
NM_001122607.1:c.286G>C
ENST00000300305.7:c.367G>C
ENST00000344691.8:c.286G>C
ENST00000358356.9:c.286G>C
ENST00000399237.6:c.331G>C
ENST00000399240.5:c.286G>C
ENST00000437180.5:c.367G>C
ENST00000455571.5:c.328G>C
ENST00000482318.5:c.74G>C

Uncertain Significance

Met criteria codes 3
PP3 PS4_Supporting PM1_Supporting
Not Met criteria codes 15
PS1 PS3 PP1 PM2 PM6 PM5 PM4 BA1 PVS1 BS3 BS1 BS4 BP4 BP2 BP7

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.367G>C (p.Asp123His) missense variant has a REVEL score >0.75 (0.943) (PP3). This variant affects one of the other residues (AA 105-204; not established as a hot spot by the MM-VCEP) within the RHD PM1_Supporting). The variant has been reported in one proband meeting at least one of the RUNX1-phenotypic criteria (PS4_Supporting; PMID: 18723428). 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: PP3, PM1_Supporting, PS4_Supporting.
Met criteria codes
PP3
REVEL: 0.943 >0.75
PS4_Supporting
1 affected family with moderate thrombocytopenia.
II-1(Pos): Moderate thrombocytopenia dx in childhood; lifetime thrombocytopenia, easy bruising (hx dx as chronic ITP); MDS dx 49 II-2(Pos): Moderate thrombocytopenia dx in childhood; MDS dx45 PubMed:18723428
PM1_Supporting
Residue in RUNT domain (105-204aa).
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
Given the unspecific phenotypes of III-2 and III-3 and being conservative, did not meet 3 meioses.
Given the unspecific phenotypes of III-2 and III-3 and being conservative, did not meet 3 meioses. PubMed:18723428
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
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
BA1
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
BS3
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
Given the unspecific phenotypes of III-2 and III-3 and being conservative, did not meet 3 meioses. PubMed:18723428
BP4
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
BP7
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
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