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.249C>G (p.Ala83=)

CA10014563

770248 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 47187013-7f50-4306-8a20-d457eaa0836f

HGVS expressions

NM_001754.5:c.249C>G

NM_001754.5(RUNX1):c.249C>G (p.Ala83=)

NC_000021.9:g.34886945G>C

CM000683.2:g.34886945G>C

NC_000021.8:g.36259242G>C

CM000683.1:g.36259242G>C

NC_000021.7:g.35181112G>C

NG_011402.2:g.1102767C>G

ENST00000675419.1:c.249C>G

ENST00000300305.7:c.249C>G

ENST00000344691.8:c.168C>G

ENST00000358356.9:c.168C>G

ENST00000399237.6:c.213C>G

ENST00000399240.5:c.168C>G

ENST00000437180.5:c.249C>G

ENST00000455571.5:c.210C>G

ENST00000482318.5:c.59-6232C>G

NM_001001890.2:c.168C>G

NM_001122607.1:c.168C>G

NM_001754.4:c.249C>G

NM_001001890.3:c.168C>G

NM_001122607.2:c.168C>G

Likely Benign

BP4 BP7

PS4 PS2 PS1 PS3 PP1 PP4 PP3 PP2 PM5 PM1 PM3 PM4 PM6 PM2 PVS1 BA1 BS2 BS4 BS3 BS1 BP2 BP3 BP1 BP5

Evidence Links 0

Expert Panel

Myeloid Malignancy VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Myeloid Malignancy VCEP

NM_001754.5(RUNX1):c.249C>G (p.Ala83=) is a synonymous variant. Evolutionary conservation prediction algorithms predict the site as not being conserved (phyloP 0.324528 is <2.0) meeting BP7. This variant is a synonymous variant therefore no REVEL score is applicable and Splice is ≤0.20 (0.00) meeting BP4. 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: BP7 and BP4.

BP4

This variant is a synonymous variant therefore no REVEL score is applicable and Splice is ≤0.20 (0.00)

BP7

Evolutionary conservation prediction algorithms predict the site as not being conserved (phyloP 0.324528 is <2.0)

PS4

Prevalence not higher in comparison to controls

PS2

Case studies not found

PS1

Amino acid location has not been established as a pathogenic variant

PS3

No functional studies found

PP1

No case studies found

PP4

This rule is not applicable for the MMVCEP

PP3

This variant is a synonymous variant therefore no REVEL score is applicable and Splice is not ≥0.38 (0.00)

PP2

This rule is not applicable for the MMVCEP

PM5

Not a missense variant

PM1

Not a missense variant

PM3

This rule is not applicable for the MMVCEP

PM4

Not an in-frame deletion/insertion

PM6

Case studies not found

PM2

Variant present in v2 (not v3) of gnomAD but does meet code criteria

PVS1

Not a null variant

BA1

Variant present in v2 (not v3) of gnomAD but does meet code criteria

BS2

This rule is not applicable for the MMVCEp

BS4

No case studies found

BS3

No functional studies found

BS1

Variant present in v2 (not v3) of gnomAD but does meet code criteria

BP2

No homozygotes present in gnomAD v2 or v3

BP3

This rule is not applicable for the MMVCEp

BP1

This rule is not applicable for the MMVCEP

BP5

This rule is not applicable for the MMVCEP

Approved on: 2022-02-14

Published on: 2022-07-05

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