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.1317C>G (p.Ser439=)

Curation Version - 1.0
Curation History
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CA512341055

1585214 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 98e0fc43-c2f5-4b1c-a073-67deaaf47a2e

Approved on: 2024-09-25

Published on: 2024-09-25

HGVS expressions

NM_001754.5:c.1317C>G

NM_001754.5(RUNX1):c.1317C>G (p.Ser439=)

NC_000021.9:g.34792261G>C

CM000683.2:g.34792261G>C

NC_000021.8:g.36164558G>C

CM000683.1:g.36164558G>C

NC_000021.7:g.35086428G>C

NG_011402.2:g.1197451C>G

ENST00000675419.1:c.1317C>G

ENST00000300305.7:c.1317C>G

ENST00000344691.8:c.1236C>G

ENST00000399240.5:c.1044C>G

ENST00000437180.5:c.1317C>G

ENST00000482318.5:c.*907C>G

NM_001001890.2:c.1236C>G

NM_001754.4:c.1317C>G

NM_001001890.3:c.1236C>G

Likely Benign

PM2_Supporting BP7 BP4

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

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.1317C>G (p.Ser439=) is a synonymous variant which has a REVEL score < 0.50 (0) and a SpliceAI score ≤ 0.20 (0) (BP4). Evolutionary conservation algorithms predict the site as not being conserved (PhyloP score ≤ 2.0 (-1.3)) (BP7). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting). In summary, this variant meets criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BP4, BP7, PM2_supporting.

PM2_Supporting

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

BP7

This variant has a SpliceAI score ≤ 0.20 (0) and evolutionary conservation prediction algorithms predict the site as not being conserved (PhyloP score ≤ 2.0 (-1.3)) (BP7).

BP4

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

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 different missense change determined to be pathogenic at this amino acid residue.

BA1

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

PP1

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

PP4

This rule is not applicable for MM-VCEP.

PP3

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

PP2

This rule is not applicable for MM-VCEP.

PM1

This variant is not a missense variant.

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.

PM6

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

PVS1

This variant is not a null variant.

BS4

Segregation was not found to be absent in two or more informative meiosis.

BS3

This variant has not been featured in in vitro or in vivo functional studies that show no damaging effect on protein function or splicing.

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 MM-VCEP.

BP5

This rule is not applicable for MM-VCEP.

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 MM-VCEP.

BP1

This rule is not applicable for MM-VCEP.

Curation History

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