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
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_001754.5(RUNX1):c.35C>G (p.Ser12Trp)

CA410208239

2754122 (ClinVar)

Gene: RUNX1
Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 9268bf0c-f422-4158-ac3b-12e2b104a60c
Approved on: 2024-10-29
Published on: 2024-10-29

HGVS expressions

NM_001754.5:c.35C>G
NM_001754.5(RUNX1):c.35C>G (p.Ser12Trp)
NC_000021.9:g.35048865G>C
CM000683.2:g.35048865G>C
NC_000021.8:g.36421162G>C
CM000683.1:g.36421162G>C
NC_000021.7:g.35343032G>C
NG_011402.2:g.940847C>G
ENST00000675419.1:c.35C>G
ENST00000300305.7:c.35C>G
ENST00000416754.1:c.35C>G
ENST00000437180.5:c.35C>G
ENST00000455571.5:c.35C>G
ENST00000475045.6:c.35C>G
ENST00000482318.5:c.35C>G
NM_001754.4:c.35C>G
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Uncertain Significance

Met criteria codes 1
PM2_Supporting
Not Met criteria codes 25
PVS1 BA1 BS4 BS3 BS1 BS2 BP5 BP7 BP2 BP3 BP4 BP1 PS3 PS2 PS4 PS1 PP4 PP1 PP3 PP2 PM1 PM3 PM4 PM5 PM6

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

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Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Myeloid Malignancy VCEP
NM_001754.5(RUNX1):c.35C>G (p.Ser12Trp) is a missense variant which is absent from gnomAD v2, v3, and v4.1 (PM2_supporting). This variant has not been reported in the literature. The computational predictor REVEL gives a score of 0.631, which is neither above nor below the thresholds predicting a damaging or benign impact on RUNX1 function, and the splice site predictor SpliceAI indicates that the variant has no impact on splicing. In summary, this variant meets the criteria to be classified as a VUS for autosomal dominant hereditary thrombocytopenia and hematologic cancer predisposition syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen Myeloid Malignancy VCEP: PM2_supporting.
Met criteria codes
PM2_Supporting
Completely absent from gnomAD v2+v3+v4 with a mean coverage of at least 20X.
Not Met criteria codes
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
Completely absent from gnomAD v2+v3+v4 with a mean coverage of at least 20X.
BS4
No 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
Completely absent from gnomAD v2+v3+v4 with a mean coverage of at least 20X.
BS2
Not applicable
BP5
Not applicable
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
BP3
Not applicable
BP4
REVEL score = 0.631, 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
PS3
No literature was found in LOVD, HGMD, ClinVar, COSMIC, Mastermind, and Google/Google Scholar searches.
PS2
No cases found in literature search, including LOVD, HGMD, ClinVar, COSMIC, Mastermind, and Google/Google Scholar searches.
PS4
No cases found in literature search, including LOVD, HGMD, ClinVar, COSMIC, Mastermind, and Google/Google Scholar searches.
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP4
Not applicable
PP1
No cases found in literature search, including LOVD, HGMD, ClinVar, COSMIC, Mastermind, and Google/Google Scholar searches.
PP3
REVEL score = 0.631, 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
PM1
Not located at a hotspot (R107, K110, A134, R162, R166, S167, R169, G170, K194, T196, D198, R210, R204) or within residues 89-204.
PM3
Not applicable
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM5
S12 variants are reported in COSMIC and/or Mastermind, but not at a high enough frequency that they would be likely classified as LP/P.
PM6
No cases found in literature search, including LOVD, HGMD, ClinVar, COSMIC, Mastermind, and Google/Google Scholar searches.
Curation History
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