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]
Link to SEPIO compliant JSON-LD document
  • See Evidence submitted by expert panel for details.

Variant: NM_001754.4(RUNX1):c.467C>A (p.Ala156Glu)

CA248628

14471 (ClinVar)

Gene: RUNX1
Condition: hereditary thrombocytopenia with normal platelets-hematological cancer predisposition syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 1023c045-33cc-4c4b-9297-ea4832be8def

HGVS expressions

NM_001754.4:c.467C>A
NM_001754.4(RUNX1):c.467C>A (p.Ala156Glu)
NC_000021.9:g.34880598G>T
CM000683.2:g.34880598G>T
NC_000021.8:g.36252895G>T
CM000683.1:g.36252895G>T
NC_000021.7:g.35174765G>T
NG_011402.2:g.1109114C>A
NM_001001890.2:c.386C>A
NM_001122607.1:c.386C>A
ENST00000300305.7:c.467C>A
ENST00000344691.8:c.386C>A
ENST00000358356.9:c.386C>A
ENST00000399237.6:c.431C>A
ENST00000399240.5:c.386C>A
ENST00000437180.5:c.467C>A
ENST00000482318.5:c.*57C>A

Likely Pathogenic

Met criteria codes 5
PS4_Supporting PP1_Strong PP3 PM2 PM1_Supporting
Not Met criteria codes 13
PS1 PS3 PVS1 BP7 BP4 BP2 BA1 PM6 PM5 PM4 BS3 BS1 BS4

Evidence Links 2

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Myeloid Malignancy VCEP
The NM_001754.4:c.467C>A (p.Ala156Glu) variant was found to co-segregate with disease in multiple affected family members, with seven meioses observed in one family (PP1_Strong; PMID: 19357396, 27112265). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2). It affects one of the residues (AA 105-204) within the RHD (PM1_Supporting). This missense variant has a REVEL score >0.75 (0.906) (PP3). It has been reported in one proband meeting at least one of the RUNX1-phenotypic criteria (PS4_ Supporting; PMID: 19357396, 27112265). In summary, this variant meets criteria to be classified as likely pathogenic. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PP1_Strong, PM2, PP3, PM1_Supporting, PS4_Supporting.
Met criteria codes
PS4_Supporting
1 affected proband in a family with FPD/AML (PMID: 19357396, PMID: 27112265).
1 affected proband in a family with FPD/AML (Pedigree 1). PubMed:19357396
The same family (Pedigree B) reported in PMID: 19357396. PubMed:27112265
PP1_Strong
8 affected individuals in one pedigree with 7 meioses.
8 affected individuals in one pedigree (Pedigree 1) with 7 meioses. PubMed:19357396
The same family (Pedigree B) reported in PMID: 19357396. PubMed:27112265
PP3
REVEL: 0.906 >0.75
PM2
The variant is absent from all population databases.
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
PVS1
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
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
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
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
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
8 affected individuals in one pedigree (Pedigree 1) with 7 meioses. PubMed:19357396
The same family (Pedigree B) reported in PMID: 19357396. PubMed:27112265
Approved on: 2019-07-30
Published on: 2019-08-02
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