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.1215G>C (p.Leu405=)

Curation Version - 1.0
Curation History
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CA512341220

1571893 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 18415086-d3a8-4531-868a-f4a391fde70b

Approved on: 2024-09-18

Published on: 2024-09-18

HGVS expressions

NM_001754.5:c.1215G>C

NM_001754.5(RUNX1):c.1215G>C (p.Leu405=)

NC_000021.9:g.34792363C>G

CM000683.2:g.34792363C>G

NC_000021.8:g.36164660C>G

CM000683.1:g.36164660C>G

NC_000021.7:g.35086530C>G

NG_011402.2:g.1197349G>C

ENST00000675419.1:c.1215G>C

ENST00000300305.7:c.1215G>C

ENST00000344691.8:c.1134G>C

ENST00000399240.5:c.942G>C

ENST00000437180.5:c.1215G>C

ENST00000482318.5:c.*805G>C

NM_001001890.2:c.1134G>C

NM_001754.4:c.1215G>C

NM_001001890.3:c.1134G>C

Likely Benign

BP7 BP4 PM2_Supporting

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

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.1215G>C (p.Leu405=) is a synonymous variant which has a SpliceAI score ≤ 0.20 (0) (BP4). This variant has a SpliceAI score ≤ 0.20 (0.00) and evolutionary conservation algorithms predict the site as not being conserved (PhyloP score ≤ 2.0 (0.00)) (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.

BP7

This variant has a SpliceAI score ≤ 0.20 (0.00) and evolutionary conservation prediction algorithms predict the site as not being conserved (PhyloP score ≤ 2.0 (0.00)) (BP7).

BP4

This synonymous variant has a SpliceAI score ≤ 0.20 (0)

PM2_Supporting

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

PS1

This variant is not a missense variant.

PS2

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

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.

PS4

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

BP5

This rule is not applicable for MM-VCEP.

BP3

This rule is not applicable for MM-VCEP.

BP1

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.

PP1

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

PP2

This rule is not applicable for MM-VCEP.

PP3

This variant does not have applicable in-silico data available.

PP4

This rule is not applicable for MM-VCEP.

PVS1

This variant is not a null variant.

PM1

This variant is not a missense variant.

PM3

This rule is not applicable for MM-VCEP.

PM5

This variant is not a missense variant.

PM4

This variant is not an in-frame deletion/insertion.

PM6

This variant does not have two or more assumed de novo occurrences in the literature.

BA1

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

BS2

This rule is not applicable for MM-VCEP.

BS1

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

BS4

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

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.

Curation History

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