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 computer assertion could be determined for this classification!

Variant: NM_001754.5(RUNX1):c.1253T>G (p.Met418Arg)

CA10014190

409805 (ClinVar)

Gene: RUNX1
Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: db0d38a9-6ebc-4782-ac3a-300d30dc1ab5
Approved on: 2024-08-12
Published on: 2024-08-12

HGVS expressions

NM_001754.5:c.1253T>G
NM_001754.5(RUNX1):c.1253T>G (p.Met418Arg)
NC_000021.9:g.34792325A>C
CM000683.2:g.34792325A>C
NC_000021.8:g.36164622A>C
CM000683.1:g.36164622A>C
NC_000021.7:g.35086492A>C
NG_011402.2:g.1197387T>G
ENST00000675419.1:c.1253T>G
ENST00000300305.7:c.1253T>G
ENST00000344691.8:c.1172T>G
ENST00000399240.5:c.980T>G
ENST00000437180.5:c.1253T>G
ENST00000482318.5:c.*843T>G
NM_001001890.2:c.1172T>G
NM_001754.4:c.1253T>G
NM_001001890.3:c.1172T>G
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Uncertain Significance

Not Met criteria codes 26
BA1 PS1 PS2 PS3 PS4 PP1 PP4 PP3 PP2 PVS1 PM5 PM3 PM1 PM4 PM6 PM2 BS4 BS3 BS1 BS2 BP5 BP7 BP2 BP3 BP4 BP1

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.1253T>G (p.Met418Arg) is a 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
BA1
gnomAD (v2): ALL: 0.006908% (13/188200) - NFE: 0.009086% (7/77040) - FIN: 0.02373% (4/16858) - OTH: 0.03631% (12/5508) gnomAD (v3): ALL: - NFE: 0.007636% (5/65476) - FIN: 0.1060% (10/9436) - SAS: 0.05126% (2/3902) - OTH: 0.04946% (1/2022) - EAS: 0.02475% (1/4040) - AFR: 0.002514% (1/39780) Highest MAF in continental population in gnomAD v2+v3 : NFE: 0.008593% (11/128010) - ALL: 0.008360% (25/299032)
PS1
No relevant cases found in literature search, including LOVD, HGMD, ClinVar, COSMIC, Mastermind, and Google/Google Scholar searches.
PS2
No relevant cases found in literature search, including LOVD, HGMD, ClinVar, COSMIC, Mastermind, and Google/Google Scholar searches.
PS3
No functional data was found in LOVD, HGMD, ClinVar, COSMIC, Mastermind, and Google/Google Scholar searches.
PS4
The variant has been reported in a Scandinavian patient with a significant bleeding assessment tool score but their platelet count was 228 x 10^9 (PMID: 28748566 - Supplementary Table 2).
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 = 0.587, 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
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM5
M418V/M391V has been reported the most in COSMIC and/or Mastermind, but it has been classified as a likely benign variant by the ClinGen MM-VCEP.
PM3
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.
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM6
No relevant cases found in literature search, including LOVD, HGMD, ClinVar, COSMIC, Mastermind, and Google/Google Scholar searches.
PM2
gnomAD (v2): ALL: 0.006908% (13/188200) - NFE: 0.009086% (7/77040) - FIN: 0.02373% (4/16858) - OTH: 0.03631% (12/5508) gnomAD (v3): ALL: - NFE: 0.007636% (5/65476) - FIN: 0.1060% (10/9436) - SAS: 0.05126% (2/3902) - OTH: 0.04946% (1/2022) - EAS: 0.02475% (1/4040) - AFR: 0.002514% (1/39780) Highest MAF in continental population in gnomAD v2+v3 : NFE: 0.008593% (11/128010) - ALL: 0.008360% (25/299032)
BS4
No relevant cases found in literature search, including LOVD, HGMD, ClinVar, COSMIC, Mastermind, and Google/Google Scholar searches.
BS3
No functional data was found in LOVD, HGMD, ClinVar, COSMIC, Mastermind, and Google/Google Scholar searches.
BS1
gnomAD (v2): ALL: 0.006908% (13/188200) - NFE: 0.009086% (7/77040) - FIN: 0.02373% (4/16858) - OTH: 0.03631% (12/5508) gnomAD (v3): ALL: - NFE: 0.007636% (5/65476) - FIN: 0.1060% (10/9436) - SAS: 0.05126% (2/3902) - OTH: 0.04946% (1/2022) - EAS: 0.02475% (1/4040) - AFR: 0.002514% (1/39780) Highest MAF in continental population in gnomAD v2+v3 : NFE: 0.008593% (11/128010) - ALL: 0.008360% (25/299032)
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 = 0.587, 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
Curation History
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