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.1145C>G (p.Pro382Arg)

CA410147964

1397177 (ClinVar)

Gene: RUNX1 (HGNC:861)

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome (MONDO:0011071)

Inheritance Mode: Autosomal dominant inheritance

UUID: fbedb105-5b65-4444-be1c-7f86b8c491a1

Approved on: 2024-10-29

Published on: 2024-10-29

HGVS expressions

NM_001754.5(RUNX1):c.1145C>G (p.Pro382Arg)

NM_001754.5:c.1145C>G

NC_000021.9:g.34792433G>C

CM000683.2:g.34792433G>C

NC_000021.8:g.36164730G>C

CM000683.1:g.36164730G>C

NC_000021.7:g.35086600G>C

NG_011402.2:g.1197279C>G

ENST00000675419.1:c.1145C>G

ENST00000300305.7:c.1145C>G

ENST00000344691.8:c.1064C>G

ENST00000399240.5:c.872C>G

ENST00000437180.5:c.1145C>G

ENST00000482318.5:c.*735C>G

NM_001001890.2:c.1064C>G

NM_001754.4:c.1145C>G

NM_001001890.3:c.1064C>G

Uncertain Significance

PP3 PM2_Supporting

PS2 PS3 PS1 BA1 PP1 PM1 PM5 PM4 PM6 BS4 BS3 BS1 BP2 BP4 PVS1 BP7

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.1145C>G (p.Pro382Arg) is a missense variant which is absent from all population databases, including gnomAD v2.1.1 and gnomAD v3.1.2, both of which provide coverage of at least 20x for the RUNX1 gene at this genomic position (PM2_supporting). This missense variant has a REVEL score >0.88 (0.942) (PP3). To our knowledge, this variant has not been reported before, and there are no other pathogenic or likely pathogenic amino acid changes affecting the same residue. 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, PP3.

PP3

This missense variant has a REVEL score >0.88 (0.942) (PP3).

PM2_Supporting

This variant is completely absent from all population databases (gnomAD v2.1.1, v3.1.2, and v4.0.0) with at least 20x coverage for RUNX1 (PM2_supporting).

PS2

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.

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.

PM1

This rule cannot be applied since this missense variant affects amino acid residue 382, which is out of RHD or residues 89-204

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.

PM4

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

PM6

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

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.

BP2

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

BP4

This rule cannot be applied since this missense variant does not have a REVEL score <0.50 (0.942).

PVS1

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

BP7

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

Curation History

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