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.1400C>A (p.Ala467Glu)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA410146806

463983 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: ce0016e0-4c01-4ac9-8859-fe7b3348533e

Approved on: 2024-07-11

Published on: 2024-07-11

HGVS expressions

NM_001754.5:c.1400C>A

NM_001754.5(RUNX1):c.1400C>A (p.Ala467Glu)

NC_000021.9:g.34792178G>T

CM000683.2:g.34792178G>T

NC_000021.8:g.36164475G>T

CM000683.1:g.36164475G>T

NC_000021.7:g.35086345G>T

NG_011402.2:g.1197534C>A

ENST00000675419.1:c.1400C>A

ENST00000300305.7:c.1400C>A

ENST00000344691.8:c.1319C>A

ENST00000399240.5:c.1127C>A

ENST00000437180.5:c.1400C>A

ENST00000482318.5:c.*990C>A

NM_001001890.2:c.1319C>A

NM_001754.4:c.1400C>A

NM_001001890.3:c.1319C>A

Uncertain Significance

BP4

PVS1 PS2 PS4 PS3 PS1 BA1 PP1 PP4 PP3 PP2 PM6 PM2 PM1 PM5 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.1400C>A (p.Ala467Glu) is a missense variant which has a REVEL score ≤0.50 (0.09) and a SpliceAI score ≤ 0.20 (0.00) (BP4). 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: BP4.

BP4

This missense variant has a REVEL score ≤0.50 (0.09) and a SpliceAI score ≤ 0.20 (0.00).

PVS1

This variant has not been featured in in vitro or in vivo functional studies showing a damaging effect on the gene or gene product.

PS2

This variant has not been found to co-segregate with the disease in the literature.

PS4

This variant has not been reported in probands.

PS3

This variant has not been featured in in vitro or in vivo functional studies showing a damaging effect on the gene or gene product.

PS1

There has not yet been a missense change determined to be pathogenic at this amino acid residue.

BA1

Highest MAF is less than 0.0015 (0.15%) at 0.00004 (0.004%, 1/24686,) in the Latino subpopulation of gnomAD v2 cohort

PP1

This variant was not found to co-segregate with disease in multiple affected family members.

PP4

This rule is not applicable for the MM-VCEP

PP3

This missense variant does not have a REVEL score >0.88 (0.085)

PP2

This rule is not applicable for the MM-VCEP

PM6

This variant has not been reported in probands in the literature.

PM2

Variant is present in database (gnomAD) with at least 20x coverage for RUNX1: 0.00004 (0.004%, 1/24686) in the Latino subpopulation of gnomAD v2 cohort

PM1

This variant does not affect any of the following amino acid residues, nor is it located within the RHD: R107, K110, A134, R162, R166, S167, R169, G170, K194, T196, D198, R201, R204 NOR is it within residues 89-204

PM5

There has not yet been a different missense change determined to be pathogenic at this amino acid residue.

PM3

This rule is not applicable for the MM-VCEP

PM4

This variant does not affect one of the other residues within the RHD.

BS4

This variant has not been reported in affected family members.

BS3

This variant has not been featured in in vitro or in vivo functional studies that show no damaging effect on protein function or splicing.

BS1

Highest MAF of 0.00004 (0.004%, 1/24686,) in the Latino subpopulation of gnomAD v2 cohort is less than 0.00015 (0.15%)

BS2

This rule is not applicable for the MM-VCEP

BP7

This variant is not a synonymous or intronic variant.

BP5

This rule is not applicable for the MM-VCEP

BP2

This variant has not been detected in a homozygous state in an individual or in a population database (gnomAD).

BP3

This rule is not applicable for the MM-VCEP

BP1

This rule is not applicable for the MM-VCEP

Curation History

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