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]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data

Variant: NM_001754.5(RUNX1):c.620G>A (p.Arg207Gln)

CA410207199

843240 (ClinVar)

Gene: RUNX1
Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: dea8e289-bfca-4936-8523-04a1c4458c16
Approved on: 2025-02-24
Published on: 2025-02-24

HGVS expressions

NM_001754.5:c.620G>A
NM_001754.5(RUNX1):c.620G>A (p.Arg207Gln)
NC_000021.9:g.34834595C>T
CM000683.2:g.34834595C>T
NC_000021.8:g.36206892C>T
CM000683.1:g.36206892C>T
NC_000021.7:g.35128762C>T
NG_011402.2:g.1155117G>A
ENST00000675419.1:c.620G>A
ENST00000300305.7:c.620G>A
ENST00000344691.8:c.539G>A
ENST00000358356.9:c.539G>A
ENST00000399237.6:c.584G>A
ENST00000399240.5:c.532+24879G>A
ENST00000437180.5:c.620G>A
ENST00000469087.1:n.156G>A
ENST00000482318.5:c.*210G>A
NM_001001890.2:c.539G>A
NM_001122607.1:c.539G>A
NM_001754.4:c.620G>A
NM_001001890.3:c.539G>A
NM_001122607.2:c.539G>A
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Uncertain Significance

Not Met criteria codes 25
PVS1 PS4 PS2 PS3 PS1 BA1 PP1 PP4 PP3 PP2 PM5 PM1 PM4 PM3 PM6 PM2 BS4 BS3 BS1 BS2 BP7 BP4 BP1 BP3 BP2

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen Myeloid Malignancy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines Version 2

PDF
Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Myeloid Malignancy VCEP
NM_001754.5(RUNX1):c.620G>A (p.Arg207Gln) is a missense variant which does not meet any ACMG/AMP criteria. 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: None.
Not Met criteria codes
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
The likely germline variant was identified in buccal cells from an 81yo male with AML whose family history was negative for bleeding history, thrombocytopenia, or other hematologic problems (PMID: 23753029). Additionally, the variant has been reported in other cases of myeloid neoplasm without germline confirmation (PMID: 29146900; PMID: 36436542). Finally, the somatic/likely somatic variant has been reported in myeloid neoplasms and solid tumors (PMID: 31772163; PMID: 32619037; PMID: 36219880; PMID: 25790293; PMID: 29420467; PMID: 30072744; DepMap Portal/CCLE).
PS2
No relevant cases found in literature search, including LOVD, HGMD, ClinVar, COSMIC, Mastermind, and Google/Google Scholar searches.
PS3
No literature was found in LOVD, HGMD, ClinVar, COSMIC, Mastermind, and Google/Google Scholar searches.
PS1
No relevant cases found in literature search, including LOVD, HGMD, ClinVar, COSMIC, Mastermind, and Google/Google Scholar searches.
BA1
- gnomAD (v2): ALL: 0.0004008% (1/249522) - NFE: 0.0008899% (1/112370) - gnomAD (v3): Completely absent with a mean coverage of at least 20X
PP1
No relevant cases found in literature search, including LOVD, HGMD, ClinVar, COSMIC, Mastermind, and Google/Google Scholar searches.
PP4
Not applicable
PP3
REVEL score = 0.801, which is not higher than the v2 threshold of 0.88. SpliceAI doesn't predict any significant splicing impact (Δ scores ≤ 0.20).
PP2
Not applicable
PM5
R207/R180 variants are reported in COSMIC and/or Mastermind, but not at a high enough frequency that they would be likely classified as LP/P.
PM1
Not located at a hotspot (R107, K110, A134, R162, R166, S167, R169, G170, K194, T196, D198, R210, R204) or within residues 89-204.
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM3
Not applicable
PM6
No relevant cases found in literature search, including LOVD, HGMD, ClinVar, COSMIC, Mastermind, and Google/Google Scholar searches.
PM2
- gnomAD (v2): ALL: 0.0004008% (1/249522) - NFE: 0.0008899% (1/112370) - gnomAD (v3): Completely absent with a mean coverage of at least 20X
BS4
No relevant cases found in literature search, including LOVD, HGMD, ClinVar, COSMIC, Mastermind, and Google/Google Scholar searches.
BS3
No literature was found in LOVD, HGMD, ClinVar, COSMIC, Mastermind, and Google/Google Scholar searches.
BS1
- gnomAD (v2): ALL: 0.0004008% (1/249522) - NFE: 0.0008899% (1/112370) - gnomAD (v3): Completely absent with a mean coverage of at least 20X
BS2
Not applicable
BP7
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP4
REVEL score = 0.801, which is not less than the v2 threshold of 0.50. SpliceAI doesn't predict any significant splicing impact (Δ scores ≤ 0.20).
BP1
Not applicable
BP3
Not applicable
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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