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_001754.4(RUNX1):c.601C>T (p.Arg201Ter)

CA16602487

376018 (ClinVar)

Gene: RUNX1
Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 86145d7f-0d2f-4234-81b7-bd179ea8e91f
Approved on: 2024-09-04
Published on: 2024-09-04

HGVS expressions

NM_001754.4:c.601C>T
NM_001754.4(RUNX1):c.601C>T (p.Arg201Ter)
NC_000021.9:g.34859486G>A
CM000683.2:g.34859486G>A
NC_000021.8:g.36231783G>A
CM000683.1:g.36231783G>A
NC_000021.7:g.35153653G>A
NG_011402.2:g.1130226C>T
ENST00000675419.1:c.601C>T
ENST00000300305.7:c.601C>T
ENST00000344691.8:c.520C>T
ENST00000358356.9:c.520C>T
ENST00000399237.6:c.565C>T
ENST00000399240.5:c.520C>T
ENST00000437180.5:c.601C>T
ENST00000467577.1:n.93C>T
ENST00000482318.5:c.*191C>T
NM_001001890.2:c.520C>T
NM_001122607.1:c.520C>T
NM_001001890.3:c.520C>T
NM_001122607.2:c.520C>T
NM_001754.5:c.601C>T
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Pathogenic

Met criteria codes 4
PM2_Supporting PS4 PVS1 PP1_Strong
Not Met criteria codes 22
PP4 PP3 PP2 PM6 PM3 PM4 PM1 PM5 BA1 BS2 BS1 BS4 BS3 PS2 PS3 PS1 BP5 BP7 BP2 BP4 BP1 BP3

Evidence Links 4

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
The NM_001754.4:c.601C>T (p.Arg201Ter) variant is a nonsense variant that is predicted to introduce a premature stop codon and expected to result in nonsense-mediated mRNA decay (PVS1). This variant has been reported in four probands meeting at least one of the RUNX1-phenotypic criteria (PS4; PMIDs: 10508512; 19387465; 20549580; 28513614). The variant was found to co-segregate with disease in multiple affected family members, with 14 meioses observed in across 4 families (PP1_Strong; PMID: 10508512; 19387465; 20549580; 28513614). The variant is absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting). In summary, this variant meets criteria to be classified as pathogenic. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PVS1, PS4, PP1_Strong, PM2_supporting.
Met criteria codes
PM2_Supporting
The variant is absent from all population databases.
PS4
Four probands reported in four publications (PMIDs: 10508512; 19387465; 20549580; 28513614). In each family the variant was present in at least two related individuals.
One proband reported in the publication. In the family the variant was present in at least two related individuals. PubMed:10508512
One proband reported in the publication. In the family the variant was present in at least two related individuals. PubMed:19387465
One proband reported in the publication. In the family the variant was present in at least two related individuals. PubMed:20549580
One proband reported in the publication. In the family the variant was present in at least two related individuals. PubMed:28513614
PVS1
Nonsense variant before the c.916 cutoff that predict to undergo NMD.
PP1_Strong
14 meioses observed across four published families. (PMIDs: 10508512; 19387465; 20549580; 28513614).
Not Met criteria codes
PP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP2
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
PM3
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
PM1
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
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS2
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
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
PS2
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
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP5
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
BP2
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
BP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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