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.303G>T (p.Val101=)

CA10014552

239047 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 997ae198-ae6a-441e-98eb-97f297cbc204

HGVS expressions

NM_001754.5:c.303G>T

NM_001754.5(RUNX1):c.303G>T (p.Val101=)

NC_000021.9:g.34886891C>A

CM000683.2:g.34886891C>A

NC_000021.8:g.36259188C>A

CM000683.1:g.36259188C>A

NC_000021.7:g.35181058C>A

NG_011402.2:g.1102821G>T

ENST00000675419.1:c.303G>T

ENST00000300305.7:c.303G>T

ENST00000344691.8:c.222G>T

ENST00000358356.9:c.222G>T

ENST00000399237.6:c.267G>T

ENST00000399240.5:c.222G>T

ENST00000437180.5:c.303G>T

ENST00000455571.5:c.264G>T

ENST00000482318.5:c.59-6178G>T

NM_001001890.2:c.222G>T

NM_001122607.1:c.222G>T

NM_001754.4:c.303G>T

NM_001001890.3:c.222G>T

NM_001122607.2:c.222G>T

Benign

BA1 BP7 BP4

PS2 PS4 PS3 PS1 PP1 PP4 PP3 PP2 PVS1 BS4 BS3 BS1 BS2 PM1 PM4 PM5 PM3 PM6 PM2 BP5 BP3 BP2 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.303G>T (p.Val101=) is a synonymous variant. MAF of 0.00671 (0.671%, 167/24878, 167 alleles) in the African subpopulation of the gnomAD cohort is ≥ 0.0015 (0.15%) (BA1). Not a missense variant, therefore, no REVEL score and SpliceAI is ≤0.50 (0.00) (BP4). Evolutionary conservation prediction algorithms predict the site as not being conserved (PhyloP score 1.4739 < 2.0 or the variant is the reference nucleotide in one primate and/or three mammal species) (BP7). In summary, this variant meets criteria to be classified as benign. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BA1, BP4, BP7.

BA1

MAF of 0.00671 (0.671%, 167/24878, 167 alleles) in the African subpopulation of the gnomAD cohort is ≥ 0.0015 (0.15%) (BA1).

BP7

Evolutionary conservation prediction algorithms predict the site as not being conserved (PhyloP score 1.4739 < 2.0 or the variant is the reference nucleotide in one primate and/or three mammal species) (BP7).

BP4

Not a missense variant, therefore, no REVEL score and SpliceAI is ≤0.50 (0.00) (BP4)

PS2

No case studies found

PS4

No case studies found

PS3

No functional studies found

PS1

Not a missense variant

PP1

No case studies found

PP4

This rule is not applicable for MM-VCEP

PP3

Not a missense variant, therefore, no REVEL score and SpliceAI is ≤0.50 (0.00) (BP4)

PP2

This rule is not applicable for MM-VCEP

PVS1

Not a null variant

BS4

No case studies found

BS3

No functional studies found

BS1

MAF of 0.00671 (0.671%, 167/24878, 167 alleles) in the African subpopulation of the gnomAD cohort is ≥ 0.0015 (0.15%) (BA1).

BS2

This rule is not applicable for MM-VCEP

PM1

Not a missense variant

PM4

Not an in-frame deletion/insertion

PM5

Not a missense variant

PM3

This rule is not applicable for MM-VCEP

PM6

No case studies found

PM2

MAF of 0.00671 (0.671%, 167/24878, 167 alleles) in the African subpopulation of the gnomAD cohort is ≥ 0.0015 (0.15%) (BA1).

BP5

This rule is not applicable for MM-VCEP

BP3

This rule is not applicable for MM-VCEP

BP2

No homozygotes found in gnomAD

BP1

This rule is not applicable for MM-VCEP

Approved on: 2024-06-24

Published on: 2024-06-24

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