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.1307C>T (p.Ser436Phe)

CA410147430

3666186 (ClinVar)

Gene: RUNX1 (HGNC:861)

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

Inheritance Mode: Autosomal dominant inheritance

UUID: 7011c167-79f1-46f0-8ac0-0022217229b7

Approved on: 2025-05-02

Published on: 2025-05-02

HGVS expressions

NM_001754.5:c.1307C>T

NM_001754.5(RUNX1):c.1307C>T (p.Ser436Phe)

NC_000021.9:g.34792271G>A

CM000683.2:g.34792271G>A

NC_000021.8:g.36164568G>A

CM000683.1:g.36164568G>A

NC_000021.7:g.35086438G>A

NG_011402.2:g.1197441C>T

ENST00000675419.1:c.1307C>T

ENST00000300305.7:c.1307C>T

ENST00000344691.8:c.1226C>T

ENST00000399240.5:c.1034C>T

ENST00000437180.5:c.1307C>T

ENST00000482318.5:c.*897C>T

NM_001001890.2:c.1226C>T

NM_001754.4:c.1307C>T

NM_001001890.3:c.1226C>T

Uncertain Significance

PM2_Supporting BP4

PVS1 PM6 PM1 PM5 PM3 BA1 BS4 BS3 BS1 BS2 BP7 BP5 BP2 BP3 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.947A>G (p.Glu316Gly) is a missense variant which has not been reported in any populations featured in any version of gnomAD, allowing for application of PM2_Supporting. This variant has a SpliceAI score of 0 and a REVEL score of 0.325, allowing for application of BP4. In summary, this variant meets criteria to be classified as a variant of uncertain significance. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PM2_Supporting, BP4.

PM2_Supporting

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

BP4

This missense variant has a REVEL score < 0.50 (0.325) and a SpliceAI score ≤ 0.20 (0) (BP4).

PVS1

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

PM3

This rule is not applicable for RUNX1.

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

This rule is not applicable for RUNX1.

BP7

This variant is not a synonymous or intronic variant.

BP5

This rule is not applicable for RUNX1.

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

This rule is not applicable for RUNX1.

BP1

This rule is not applicable for RUNX1.

PS2

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

PS4

The prevalence of the variant in affected individuals has not been reported to be significantly increased compared with the prevalence in controls.

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 RUNX1.

PP3

This missense variant does not have a REVEL score of ≥ 0.88 or a SpliceAI score ≥ 0.38.

PP2

This rule is not applicable for RUNX1.

Curation History

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