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]

Link to SEPIO compliant JSON-LD document

Variant: NM_001754.5(RUNX1):c.188C>T (p.Ala63Val)

CA10014572

2630595 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: d73e55e5-66e0-4bea-acc6-2356271514b6

Approved on: 2024-09-12

Published on: 2024-09-12

HGVS expressions

NM_001754.5:c.188C>T

NM_001754.5(RUNX1):c.188C>T (p.Ala63Val)

NC_000021.9:g.34887006G>A

CM000683.2:g.34887006G>A

NC_000021.8:g.36259303G>A

CM000683.1:g.36259303G>A

NC_000021.7:g.35181173G>A

NG_011402.2:g.1102706C>T

ENST00000675419.1:c.188C>T

ENST00000300305.7:c.188C>T

ENST00000344691.8:c.107C>T

ENST00000358356.9:c.107C>T

ENST00000399237.6:c.152C>T

ENST00000399240.5:c.107C>T

ENST00000437180.5:c.188C>T

ENST00000455571.5:c.149C>T

ENST00000482318.5:c.59-6293C>T

NM_001001890.2:c.107C>T

NM_001122607.1:c.107C>T

NM_001754.4:c.188C>T

NM_001001890.3:c.107C>T

NM_001122607.2:c.107C>T

Uncertain Significance

BP4 PM2_Supporting

BS2 BS4 BS3 BS1 BP2 BP3 BP1 BP7 BP5 PVS1 PS2 PS4 PS3 PS1 PP1 PP4 PP3 PP2 PM6 PM1 PM5 PM3 PM4 BA1

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.188C>T (p.Ala63Val) is a missense variant which is present in only 1 individual in gnomAD 2.0 with at least 20x coverage for RUNX1 (PM2_supporting). This missense variant has a REVEL score <0.50 (0.273) and a SpliceAI score ≤0.20 (0.01) (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, PM2_supporting.

BP4

This missense variant has a REVEL score < 0.50 (0.273) and a SpliceAI score ≤ 0.20 (0.01) (BP4).

PM2_Supporting

This variant is is only present in 1 individual in gnomAD 2.0 with at least 20x coverage for RUNX1 (PM2_Supporting).

BS2

This rule is not applicable for MM-VCEP

BS4

Segregation data for this variant has not been reported in literature

BS3

This variant has not been featured in in vitro or in vivo functional studies that show no damaging effect on the gene or gene product.

BS1

This variant does not have a MAF between 0.00015 (0.015%) and 0.0015 (0.15%) in any general continental dataset.

BP2

Information not available

BP3

This rule is not applicable for MM-VCEP

BP1

This rule is not applicable for MM-VCEP

BP7

This variant is not a synonymous or intronic variant

BP5

This rule is not applicable for MM-VCEP

PVS1

This variant is not a null variant.

PS2

This variant does not have a proven de novo occurrence in the literature.

PS4

Proband data for this variant has not been reported in literature.

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.

PP1

Segregation data for this variant has not been reported in literature

PP4

This rule is not applicable for MM-VCEP

PP3

REVEL score 0.273 Splice AI 0.01

PP2

This rule is not applicable for MM-VCEP

PM6

De novo data for this variant has not been reported in literature.

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 OR 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 MM-VCEP

PM4

This variant is not an in-frame deletion/insertion.

BA1

This variant does not have a MAF between 0.00015 (0.015%) and 0.0015 (0.15%) in any general continental dataset.

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