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.178G>C (p.Ala60Pro)

CA410204003

1000965 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: a9d70d7c-39f8-4bf4-9170-d0c436d6abbc

Approved on: 2024-09-25

Published on: 2024-09-25

HGVS expressions

NM_001754.5:c.178G>C

NM_001754.5(RUNX1):c.178G>C (p.Ala60Pro)

NC_000021.9:g.34887016C>G

CM000683.2:g.34887016C>G

NC_000021.8:g.36259313C>G

CM000683.1:g.36259313C>G

NC_000021.7:g.35181183C>G

NG_011402.2:g.1102696G>C

ENST00000675419.1:c.178G>C

ENST00000300305.7:c.178G>C

ENST00000344691.8:c.97G>C

ENST00000358356.9:c.97G>C

ENST00000399237.6:c.142G>C

ENST00000399240.5:c.97G>C

ENST00000437180.5:c.178G>C

ENST00000455571.5:c.139G>C

ENST00000482318.5:c.59-6303G>C

NM_001001890.2:c.97G>C

NM_001122607.1:c.97G>C

NM_001754.4:c.178G>C

NM_001001890.3:c.97G>C

NM_001122607.2:c.97G>C

Uncertain Significance

BP4 PM2_Supporting

BA1 PP1 PP3 PM6 PM1 PM4 PM5 PVS1 BS4 BS3 BS1 BP7 BP2 PS2 PS4 PS3 PS1

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.178G>C (p.Ala60Pro) is a missense variant which is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting). This variant has a REVEL score of 0.411, which is less than 0.50 and a spliceAI score <0.2 (0.0) (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: PM2_supporting, BP4.

BP4

This rule cannot be applied since this missense variant has not a REVEL score <0.50 (0.411). (BP4)

PM2_Supporting

This variant is completely absent from all population databases (gnomAD v2.1.1 and v3.1.2) with at least 20x coverage for RUNX1 (PM2_supporting).

BA1

This rule cannot be applied since the variant is completely absent from all population databases.

PP1

This rule cannot be applied since, to our knowledge, this variant has not been reported in any study and we have no information about its cosegregation with the disease.

PP3

This rule cannot be applied since this missense variant has not a REVEL score >0.88 (0.411).

PM6

This rule cannot be applied since, to our knowledge, this variant has not been reported in any study.

PM1

This rule cannot be applied since this missense variant affects amino acid residue 60, which is out of RHD or residues 89-204.

PM4

This rule cannot be applied since this is a missense variant.

PM5

This rule cannot be applied because, to our knowledge, this missense variant does not impact an amino acid residue where a different pathogenic missense change has previously been observed.

PVS1

This rule cannot be applied since this is a missense variant.

BS4

This rule cannot be applied since, to our knowledge, this variant has not been reported in any study and we have no information about segregation.

BS3

To our knowledge, no in vitro or in vivo functional studies are available for this variant.

BS1

This rule cannot be applied since the variant is completely absent from all population databases.

BP7

This rule cannot be applied since this is a missense variant.

BP2

This rule cannot be applied since, to our knowledge, this variant has not been reported in any study.

PS2

This rule cannot be applied since, to our knowledge, this variant has not been reported in any study.

PS4

This rule cannot be applied since, to our knowledge, this variant has not been reported in any study.

PS3

To our knowledge, no in vitro or in vivo functional studies are available for this variant.

PS1

This rule cannot be applied because, to our knowledge, this missense variant does not generate the same amino acid change as a previously identified pathogenic variant regardless of nucleotide change.

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