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_001754.5(RUNX1):c.1415T>C (p.Leu472Pro)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA10014174

463984 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 2b491571-516e-4909-a1ca-1d034807cf15

Approved on: 2022-04-08

Published on: 2022-06-30

HGVS expressions

NM_001754.5:c.1415T>C

NM_001754.5(RUNX1):c.1415T>C (p.Leu472Pro)

NC_000021.9:g.34792163A>G

CM000683.2:g.34792163A>G

NC_000021.8:g.36164460A>G

CM000683.1:g.36164460A>G

NC_000021.7:g.35086330A>G

NG_011402.2:g.1197549T>C

ENST00000675419.1:c.1415T>C

ENST00000300305.7:c.1415T>C

ENST00000344691.8:c.1334T>C

ENST00000399240.5:c.1142T>C

ENST00000437180.5:c.1415T>C

ENST00000482318.5:c.*1005T>C

NM_001001890.2:c.1334T>C

NM_001754.4:c.1415T>C

NM_001001890.3:c.1334T>C

Benign

BA1 BP4

PP1 PP3 PP2 PP4 PM2 PM5 PM1 PM4 PM3 PVS1 BS2 BS4 BS3 BS1 BP7 BP5 BP1 BP3 BP2 PS4 PS2 PS1 PS3

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.1415T>C (p.Leu472Pro) is a missense variant in the final exon of the protein. MAF of 0.002289 (0.2289%, 23/10046 alleles, gnomad v2.11) in South East Asian population: cohort is ≥ 0.0015 (0.15%) (BA1). The REVEL score= 0.414 (≤0.50) and SpliceAI is ≤0.20 (0.00) (BP4). In summary, this variant meets the criteria to be classified as benign. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BA1, BP4

BA1

MAF of 0.002289 (0.2289%, 23/10046 alleles, gnomad v2.11) in South East Asian population: cohort is ≥ 0.0015 (0.15%) (BA1). gnomAD (v2): MAF of 0.0001986 (0.001986%, 23/115798) gnomAD (v3): MAF of 0.00007916% (0.007916%,12/1151588)-

BP4

REVEL score= 0.414 (≤0.50) and SpliceAI is ≤0.20 (0.00) (BP4)

PP1

One affected individual in pedigree with genetic screening (PMID: 26884589,PMID: 23971860, hairy cell leukemia) -Not confirmed germline as identified in PB and buccal mucosa

PP3

BP4 met

PP2

This rule is not applicable for MM-VCEP

PP4

This rule is not applicable for MM-VCEP

PM2

BA1 Met

PM5

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

PM1

Not located at a hotspot (R107, K110, A134, R162, R166, S167, R169, G170, K194, T196, D198, R210, R204) or within residues 89-204.

PM4

Missense Variant

PM3

This rule is not applicable for MM-VCEP

PVS1

Missense Variant

BS2

This rule is not applicable for MM-VCEP

BS4

No case studies found

BS3

No evidence found

BS1

BA1 met

BP7

Missense variant

BP5

This rule is not applicable for MM-VCEP

BP1

This rule is not applicable for MM-VCEP

BP3

This rule is not applicable for MM-VCEP

BP2

No homozygotes found in gnomAD

PS4

No case studies found

PS2

Not found in literature

PS1

No literature was found in LOVD, HGMD, ClinVar, COSMIC, Mastermind, and Google/Google Scholar searches.

PS3

No evidence found

Curation History

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