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.342C>A (p.Ile114=)

CA10014548

415834 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: d37a12ac-fd91-4341-93ac-028aece5a043

Approved on: 2024-09-10

Published on: 2024-09-10

HGVS expressions

NM_001754.5:c.342C>A

NM_001754.5(RUNX1):c.342C>A (p.Ile114=)

NC_000021.9:g.34886852G>T

CM000683.2:g.34886852G>T

NC_000021.8:g.36259149G>T

CM000683.1:g.36259149G>T

NC_000021.7:g.35181019G>T

NG_011402.2:g.1102860C>A

ENST00000675419.1:c.342C>A

ENST00000300305.7:c.342C>A

ENST00000344691.8:c.261C>A

ENST00000358356.9:c.261C>A

ENST00000399237.6:c.306C>A

ENST00000399240.5:c.261C>A

ENST00000437180.5:c.342C>A

ENST00000455571.5:c.303C>A

ENST00000482318.5:c.59-6139C>A

NM_001001890.2:c.261C>A

NM_001122607.1:c.261C>A

NM_001754.4:c.342C>A

NM_001001890.3:c.261C>A

NM_001122607.2:c.261C>A

Benign

BP4 BP2 BA1

PS1 PS3 PS2 PS4 BP7 BP5 BP3 BP1 PVS1 PP3 PP2 PP4 PP1 PM5 PM1 PM4 PM3 PM6 PM2 BS3 BS4 BS1 BS2

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.342C>A (p.Ile114=) is a synonymous variant. This variant has a MAF of 0.00256 (0.256%, 47/18362, 47 alleles) in the East Asian gnomAD cohort is ≥ 0.0015 (0.15%) (BA1). Variant observed in homozygous state (1) in gnomAD v2.1.1 and v3.1.2. (BP2). This variant is not a missense variant therefore REVEL score is not applicable and SpliceAI is ≤0.50 (0.00) (BP4). 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, BP2, BP4.

BP4

Not a missense variant therefore REVEL score is not applicable and SpliceAI is ≤0.50 (0.00) (BP4).

BP2

Variant observed in homozygous state (1) in gnomAD v2.1.1 and v3.1.2. (BP2)

BA1

MAF of 0.00256 (0.256%, 47/18362, 47 alleles) in the XXXX subpopulation of the East Asian gnomAD cohort is ≥ 0.0015 (0.15%) (BA1).

PS1

Not a missense variant

PS3

No functional studies found

PS2

No case studies found

PS4

No case studies found

BP7

PhyloP = 2.14 >2.0

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

PVS1

Not a null variant

PP3

Not a missense variant therefore REVEL score is not applicable and SpliceAI is ≤0.50 (0.00) (BP4).

PP2

This rule is not applicable for MM-VCEP

PP4

This rule is not applicable for MM-VCEP

PP1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PM5

Not a missense variant

PM1

Not a missense variant

PM4

Not an inframe deletions

PM3

This rule is not applicable for MM-VCEP

PM6

No case studies found

PM2

MAF of 0.00256 (0.256%, 47/18362, 47 alleles) in the XXXX subpopulation of the East Asian gnomAD cohort is ≥ 0.0015 (0.15%) (BA1).

BS3

No functional studies found

BS4

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

BS1

MAF of 0.00256 (0.256%, 47/18362, 47 alleles) in the XXXX subpopulation of the East Asian gnomAD cohort is ≥ 0.0015 (0.15%) (BA1).

BS2

This rule is not applicable for MM-VCEP

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