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.65T>C (p.Ile22Thr)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA410205770

1471561 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 2fbd206d-a309-4a0d-b206-c7ce0fb3a737

Approved on: 2024-10-29

Published on: 2024-10-29

HGVS expressions

NM_001754.5:c.65T>C

NM_001754.5(RUNX1):c.65T>C (p.Ile22Thr)

NC_000021.9:g.34892957A>G

CM000683.2:g.34892957A>G

NC_000021.8:g.36265254A>G

CM000683.1:g.36265254A>G

NC_000021.7:g.35187124A>G

NG_011402.2:g.1096755T>C

ENST00000675419.1:c.65T>C

ENST00000300305.7:c.65T>C

ENST00000416754.1:c.65T>C

ENST00000437180.5:c.65T>C

ENST00000455571.5:c.59-5861T>C

ENST00000475045.6:c.65T>C

ENST00000482318.5:c.59-12244T>C

NM_001754.4:c.65T>C

Uncertain Significance

BP4

PS4 PS2 PS1 PS3 PP1 PP4 PP3 PP2 PM5 PM1 PM3 PM4 PM6 PM2 PVS1 BA1 BS2 BS3 BS1 BP2 BP3 BP1 BP7 BP5

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.65T>C (p.Ile22Thr) is a missense variant. This variant is present at a MAF of 0.00002915(0.002915%, 1/34310) in the Admixed American population of gnomAD v2.1.1. This missense variant has a REVEL score <0.50 (0.272)(BP4). No probands meeting RUNX1 FPDMM phenotypic criteria have been described with this variant. 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

BP4

This missense variant has a REVEL score <0.50 (0.272).

PS4

No proband meeting RUNX1 FPD-MM phenotypic criteria has been described

PS2

No case study found

PS1

Amino Acid 22 has not been determined to be pathogenic previously

PS3

No functional Studies Found

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

PM5

Amino Acid 22 has not been determined to be pathogenic previously

PM1

Amino acid 22 is outside of the mutational hotspot (AA 89-204)

PM3

This rule is not applicable for MM-VCEP

PM4

This is a missense variant

PM6

No case study found

PM2

This variant is present at a MAF of 0.00002915(0.002915%, 1/34310) in the Admixed American population of gnomAD v2.1.1

PVS1

This is not a null variant

BA1

This variant is present at a MAF of 0.00002915(0.002915%, 1/34310) in the Admixed American population of gnomAD v2.1.1

BS2

This rule is not applicable for MM-VCEP

BS3

No functional Studies Found

BS1

This variant is present at a MAF of 0.00002915(0.002915%, 1/34310) in the Admixed American population of gnomAD v2.1.1

BP2

No case study found

BP3

This rule is not applicable for MM-VCEP

BP1

This rule is not applicable for MM-VCEP

BP7

This is a missense variant

BP5

This rule is not applicable for MM-VCEP

Curation History

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