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]
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  • 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.619C>T (p.Arg207Trp)

CA410207207

436615 (ClinVar)

Gene: RUNX1
Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 95726ced-7a76-4641-b7f9-d216ae3d38c5
Approved on: 2024-07-11
Published on: 2024-07-11

HGVS expressions

NM_001754.5:c.619C>T
NM_001754.5(RUNX1):c.619C>T (p.Arg207Trp)
NC_000021.9:g.34834596G>A
CM000683.2:g.34834596G>A
NC_000021.8:g.36206893G>A
CM000683.1:g.36206893G>A
NC_000021.7:g.35128763G>A
NG_011402.2:g.1155116C>T
ENST00000675419.1:c.619C>T
ENST00000300305.7:c.619C>T
ENST00000344691.8:c.538C>T
ENST00000358356.9:c.538C>T
ENST00000399237.6:c.583C>T
ENST00000399240.5:c.532+24878C>T
ENST00000437180.5:c.619C>T
ENST00000469087.1:n.155C>T
ENST00000482318.5:c.*209C>T
NM_001001890.2:c.538C>T
NM_001122607.1:c.538C>T
NM_001754.4:c.619C>T
NM_001001890.3:c.538C>T
NM_001122607.2:c.538C>T

Uncertain Significance

Met criteria codes 3
PS4_Supporting PP3 PM2_Supporting
Not Met criteria codes 23
PVS1 BP7 BP5 BP2 BP3 BP4 BP1 BA1 PS2 PS1 PS3 PP1 PP4 PP2 PM6 PM3 PM4 PM1 PM5 BS2 BS4 BS3 BS1

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.619C>T (p.Arg207Trp) is a missense variant which is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting). It has a REVEL score >0.75 (0.8109, PP3). This variant has been reported in one proband meeting at least one of the RUNX1-phenotypic criteria (PS4_supporting; internal laboratory data, VCV000436615.1). 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: PS4_supporting, PM2_supporting, PP3.
Met criteria codes
PS4_Supporting
Internal clinical laboratory data show that this variant was found in a patient with thrombocytopenia meeting the RUNX1-phenotype (VCV000436615.1).
PP3
This missense variant has a REVEL score < 0.50 (X) and a SpliceAI score ≤ 0.20 (0.8109) (BP4).
PM2_Supporting
This variant is absent from gnomAD.
Not Met criteria codes
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
BP5
This rule is not applicable for MM-VCEP.
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP3
This rule is not applicable for MM-VCEP.
BP4
This missense variant does not have a REVEL score < 0.50.
BP1
This rule is not applicable for MM-VCEP.
BA1
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
PS1
There has not yet been a missense change determined to be pathogenic at this amino acid residue.
PS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP4
This rule is not applicable for MM-VCEP.
PP2
This rule is not applicable for MM-VCEP.
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM3
This rule is not applicable for MM-VCEP.
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
There has not yet been a different missense change determined to be pathogenic at this amino acid residue.
BS2
This rule is not applicable for MM-VCEP.
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
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
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