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.193G>C (p.Ala65Pro)

CA410203954

2807004 (ClinVar)

Gene: RUNX1 (HGNC:861)

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

Inheritance Mode: Autosomal dominant inheritance

UUID: e1fcab36-5b5f-4b75-80b9-329f389de224

Approved on: 2024-09-12

Published on: 2024-09-12

HGVS expressions

NM_001754.5:c.193G>C

NM_001754.5(RUNX1):c.193G>C (p.Ala65Pro)

NC_000021.9:g.34887001C>G

CM000683.2:g.34887001C>G

NC_000021.8:g.36259298C>G

CM000683.1:g.36259298C>G

NC_000021.7:g.35181168C>G

NG_011402.2:g.1102711G>C

ENST00000675419.1:c.193G>C

ENST00000300305.7:c.193G>C

ENST00000344691.8:c.112G>C

ENST00000358356.9:c.112G>C

ENST00000399237.6:c.157G>C

ENST00000399240.5:c.112G>C

ENST00000437180.5:c.193G>C

ENST00000455571.5:c.154G>C

ENST00000482318.5:c.59-6288G>C

NM_001001890.2:c.112G>C

NM_001122607.1:c.112G>C

NM_001754.4:c.193G>C

NM_001001890.3:c.112G>C

NM_001122607.2:c.112G>C

Uncertain Significance

PM2_Supporting

PVS1 PM6 PM1 PM5 PM3 PM4 BA1 BS4 BS3 BS1 BS2 BP7 BP5 BP2 BP3 BP4 BP1 PS2 PS4 PS3 PS1 PP1 PP4 PP3 PP2

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.193G>C (p.Ala65Pro) is a missense variant in exon 4. This variant has not been observed in any population according to gnomAD (PM2_Supporting). The nucleotide substitution is not predicted to disrupt splicing (SpliceAI score = 0.01). The effect of the amino acid change is uncertain, as the REVEL score of 0.545 falls between 0.5 and 0.88, and functional evidence is not available in the literature for this variant. There are no reported cases. Overall, 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.

PM2_Supporting

This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_Supporting).

PVS1

This is not a null variant;

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 are 2 other missense variants at this residue, but none have been determined to be pathogenic.

PM3

not applicable

PM4

This is not an in/del variant.

BA1

This variant does not have a MAF ≥ 0.0015 (0.15%) in any general continental population dataset.

BS4

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

BS3

In vitro or in vivo functional data has not been reported for this variant in the literature.

BS1

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

BS2

not applicable

BP7

This is not a silent variant.

BP5

not applicable

BP2

This variant has not been observed in trans with a pathogenic variant for a fully penetrant dominant gene/disorder or observed in cis with a pathogenic variant in any inheritance pattern.

BP3

not applicable

BP4

This missense variant does not have a REVEL score < 0.50 (0.545).

BP1

not applicable

PS2

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

PS4

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

PS3

In vitro or in vivo functional data has not been reported for this variant in the literature.

PS1

There has not yet been a missense change resulting in the same change in protein which has been determined to be pathogenic at this amino acid residue.

PP1

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

PP4

not applicable

PP3

This missense variant does not have a REVEL score of ≥ 0.88 (0.545).

PP2

not applicable

Curation History

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