Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_001754.5(RUNX1):c.743A>C (p.Asn248Thr)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA10014364

532670 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: a2c03be5-eaef-404d-930a-5e777df97e76

Approved on: 2024-07-25

Published on: 2024-07-25

HGVS expressions

NM_001754.5:c.743A>C

NM_001754.5(RUNX1):c.743A>C (p.Asn248Thr)

NC_000021.9:g.34834472T>G

CM000683.2:g.34834472T>G

NC_000021.8:g.36206769T>G

CM000683.1:g.36206769T>G

NC_000021.7:g.35128639T>G

NG_011402.2:g.1155240A>C

ENST00000675419.1:c.743A>C

ENST00000300305.7:c.743A>C

ENST00000344691.8:c.662A>C

ENST00000358356.9:c.662A>C

ENST00000399237.6:c.707A>C

ENST00000399240.5:c.532+25002A>C

ENST00000437180.5:c.743A>C

ENST00000469087.1:n.279A>C

ENST00000482318.5:c.*333A>C

NM_001001890.2:c.662A>C

NM_001122607.1:c.662A>C

NM_001754.4:c.743A>C

NM_001001890.3:c.662A>C

NM_001122607.2:c.662A>C

Uncertain Significance

BP4 PS4_Supporting

PVS1 PS2 PS1 PS3 BA1 PP1 PP4 PP3 PP2 PM6 PM2 PM5 PM1 PM3 PM4 BS4 BS3 BS1 BS2 BP7 BP5 BP2 BP3 BP1

Evidence Links 0

Expert Panel

Myeloid Malignancy VCEP

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.743A>C (p.Asn248Thr) is a missense variant. This variant is present in two alleles in the South Asian population at a MAF of 0.0065% in gnomAD v2.1.1. This variant has been reported in one proband meeting at least one of the RUNX1-phenotypic criteria (Thrombocytopenia) (PS4_supporting). This missense variant has a REVEL score <0.50 (0.213) (BP4). In summary, this variant meets the criteria to be classified as a variant of uncertain significance. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BP4, PS4_supporting.

BP4

This missense variant has a REVEL score <0.50 (0.213).

PS4_Supporting

One proband with thrombocytopenia

PVS1

This is not a null variant

PS2

No case study found

PS1

A missense change in amino acid 248 has not been determined to be pathogenic before

PS3

No case studies found

BA1

This variant is present at a MAF of 0.00006545 (0.0065%, 2/30560 ) in the South Asian population of gnomAD v2.1

PP1

No case study found

PP4

This rule is not applicable for MM-VCEP

PP3

BP4 Met

PP2

This rule is not applicable for MM-VCEP

PM6

No case study found

PM2

This variant is present at a MAF of 0.00006545 (0.0065%, 2/30560 ) in the South Asian population of gnomAD v2.1

PM5

A missense change in amino acid 248 has not been determined to be pathogenic before

PM1

The variant is located outside of the mutational hot spot and/or critical and well- established functional domain as defined by the MM-VCEP (AA 89-204)

PM3

This rule is not applicable for MM-VCEP

PM4

This is a missense variant

BS4

No case study found

BS3

No case studies found

BS1

This variant is present at a MAF of 0.00006545 (0.0065%, 2/30560 ) in the South Asian population of gnomAD v2.1

BS2

This rule is not applicable for MM-VCEP

BP7

No predicted splicing affects

BP5

This rule is not applicable for MM-VCEP

BP2

No case study found

BP3

This rule is not applicable for MM-VCEP

BP1

This rule is not applicable for MM-VCEP

Curation History

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