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]

Link to SEPIO compliant JSON-LD document

Variant: NM_001754.5(RUNX1):c.375A>G (p.Pro125=)

CA512318776

1635529 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 6f13fbe7-8a80-405d-8497-cd9df527ca4f

Approved on: 2024-09-18

Published on: 2024-09-18

HGVS expressions

NM_001754.5:c.375A>G

NM_001754.5(RUNX1):c.375A>G (p.Pro125=)

NC_000021.9:g.34880690T>C

CM000683.2:g.34880690T>C

NC_000021.8:g.36252987T>C

CM000683.1:g.36252987T>C

NC_000021.7:g.35174857T>C

NG_011402.2:g.1109022A>G

ENST00000675419.1:c.375A>G

ENST00000300305.7:c.375A>G

ENST00000344691.8:c.294A>G

ENST00000358356.9:c.294A>G

ENST00000399237.6:c.339A>G

ENST00000399240.5:c.294A>G

ENST00000437180.5:c.375A>G

ENST00000455571.5:c.336A>G

ENST00000482318.5:c.82A>G

NM_001001890.2:c.294A>G

NM_001122607.1:c.294A>G

NM_001754.4:c.375A>G

NM_001001890.3:c.294A>G

NM_001122607.2:c.294A>G

Likely Benign

PM2_Supporting BP4 BP7

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

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.375A>G (p.Pro125=) is a synonymous variant which has a SpliceAI score ≤ 0.20 (0.01) (BP4). This variant has a SpliceAI score ≤ 0.20 (0.01) and evolutionary conservation algorithms predict the site as being not conserved (PhyloP score ≤ 2.0 (-3.10) (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 (PM2_Supporting).

BP4

This synonymous variant has a SpliceAI score ≤ 0.20 (0.01) (BP4).

BP7

This variant has a SpliceAI score ≤ 0.20 (0.01) and evolutionary conservation prediction algorithms predict the site as not being conserved (PhyloP score ≤ 2.0 (-3.10) (BP7).

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

This variant is not a missense variant.

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 or intronic 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

This variant is not a missense variant.

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.

BS2

This rule is not applicable for MM-VCEP.

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.

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.

BP5

This rule is not applicable for MM-VCEP.

PVS1

This variant is not a null variant.

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