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_001754.4(RUNX1):c.1257G>A (p.Val419=)

Curation Version - 2.0
Curation History
JSON LD for Version 2.0

CA512341177

436611 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 45e8489f-6a97-40c0-8875-ebee7b797ef2

Approved on: 2025-01-15

Published on: 2025-01-15

HGVS expressions

NM_001754.4:c.1257G>A

NM_001754.4(RUNX1):c.1257G>A (p.Val419=)

NC_000021.9:g.34792321C>T

CM000683.2:g.34792321C>T

NC_000021.8:g.36164618C>T

CM000683.1:g.36164618C>T

NC_000021.7:g.35086488C>T

NG_011402.2:g.1197391G>A

ENST00000675419.1:c.1257G>A

ENST00000300305.7:c.1257G>A

ENST00000344691.8:c.1176G>A

ENST00000399240.5:c.984G>A

ENST00000437180.5:c.1257G>A

ENST00000482318.5:c.*847G>A

NM_001001890.2:c.1176G>A

NM_001001890.3:c.1176G>A

NM_001754.5:c.1257G>A

Likely Benign

BS1 BP4 BP7

BS2 BS4 BS3 BP2 BP3 BP1 BP5 BA1 PS2 PS4 PS3 PS1 PP4 PP1 PP3 PP2 PVS1 PM3 PM1 PM4 PM5 PM6 PM2

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.1257G>A (p.Val419=) is a synonymous variant which meets criteria for likely benign classification. The MAF is 0.0001369 (0.01369%, 7/51146 alleles) in the Admixed American subpopulation of the gnomAD v4.1.0 cohort, which is between 0.00015 (0.015%) and 0.0015 (0.15%) (BS1). It has a SpliceAI score ≤ 0.20 (Donor gain Δ score 0.01) (BP4), and evolutionary conservation algorithms predict the site as not being conserved (PhyloP score ≤ 2.0 (0.370)) (BP7). 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: BS1, BP4, BP7.

BS1

MAF of 0.0001369 (0.01369%, 7/51146, 7 alleles) in the Admixed American subpopulation of the gnomAD v4.1.0cohort is between 0.00015 (0.015%) and 0.0015 (0.15%) (BS1).

BP4

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

BP7

This variant has a SpliceAI score ≤ 0.20 (0.01) and evolutionary conservation algorithms predict the site as not being conserved (PhyloP score ≤ 2.0 (0.370) (BP7).

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.

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

BA1

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

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.

PP4

This rule is not applicable for MM-VCEP

PP1

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

PP3

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

PP2

This rule is not applicable for MM-VCEP.

PVS1

This variant is not a null variant.

PM3

This rule is not applicable for MM-VCEP

PM1

This variant is not a missense variant.

PM4

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

PM5

This variant is not a missense variant.

PM6

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

PM2

This variant is present in at least one population database.

Curation History

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