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.*3021A>G

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Curation History
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CA10650416

339816 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 769cd169-4fec-408f-a51f-8ad96420b9ec

Approved on: 2024-09-18

Published on: 2024-09-18

HGVS expressions

NM_001754.5:c.*3021A>G

NM_001754.5(RUNX1):c.*3021A>G

NC_000021.9:g.34789114T>C

CM000683.2:g.34789114T>C

NC_000021.8:g.36161411T>C

CM000683.1:g.36161411T>C

NC_000021.7:g.35083281T>C

NG_011402.2:g.1200598A>G

ENST00000675419.1:c.*3021A>G

ENST00000300305.7:c.*3021A>G

ENST00000344691.8:c.*3021A>G

ENST00000437180.5:c.*3021A>G

NM_001001890.2:c.*3021A>G

NM_001754.4:c.*3021A>G

NM_001001890.3:c.*3021A>G

Likely Benign

BS1 BP2

BS2 BS4 BS3 BP5 BP7 BP3 BP4 BP1 PS1 PS2 PS3 PS4 PP4 PP3 PP2 PP1 BA1 PM5 PM1 PM4 PM3 PM6 PM2 PVS1

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.*3021A>G is a substitution in the 3' UTR of RUNX1. Since the variant is located in the 3' UTR, it is not expected to alter the amino acid sequence. The highest continental population minor allele frequency in gnomAD v2, v3, and v4 is 0.0005834 (9/15,428), 0.0006908 (47/68,040), and 0.0007621 (90/118,088), respectively, in the non-Finnish European population (BS1). This variant has been observed in one homozygous individual of Ashkenazi Jewish descent in gnomAD v3/v4, and hereditary thrombocytopenia and hematologic cancer predisposition syndrome is a condition with full penetrance at an early age (BP2). In summary, this variant meets the criteria to be classified as likely benign for hereditary thrombocytopenia and hematologic cancer predisposition syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen Myeloid Malignancy VCEP: BS1 and BP2.

BS1

gnomAD v2: ALL: 0.004458% (14/31406) - ASJ: 1.034% (3/290) - NFE: 0.05834% (9/15428) - AFR: 0.02294% (2/8718) gnomAD v3: ALL: 0.06045% (90+2/152198) - ASJ: 0.9222% (30+2/3470) - RMG: 0.1435% (3/2090) - NFE: 0.06908% (47/68040) - SAS: 0.02070% (1/4830) - AFR: 0.01448% (6/41446) - AMR: 0.01309% (2/15280) - FIN: 0.009420% (1/10616) gnomAD v4: ALL: 0.07929% (183+2/233320) - ASJ: 0.8147% (68+2/8592) - RMG: 0.1689% (15/8882) - NFE: 0.07621% (90/118088) - SAS: 0.01809% (1/5528) - AFR: 0.01320% (6/45466) - AMR: 0.01124% (2/17800) - FIN: 0.009363% (1/10680)

BP2

One homozygous individual of Ashkenazi Jewish descent is reported in gnomAD v3/v4.

BS2

Not applicable

BS4

No relevant cases found in literature search, including LOVD, HGMD, ClinVar, COSMIC, Mastermind, and Google/Google Scholar searches.

BS3

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

BP5

Not applicable

BP7

This intronic variant is located at a nucleotide that is conserved per an evolutionary conservation algorithm (PhyloP score = -0.35252 in GRCh38), and the variant allele is the reference nucleotide in one primate and/or three mammal species.

BP3

Not applicable

BP4

SpliceAI doesn't predict any significant splicing impact (Δ scores ≤ 0.20).

BP1

Not applicable

PS1

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

PS2

No relevant cases found in literature search, including LOVD, HGMD, ClinVar, COSMIC, Mastermind, and Google/Google Scholar searches.

PS3

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

PS4

No relevant cases found in literature search, including LOVD, HGMD, ClinVar, COSMIC, Mastermind, and Google/Google Scholar searches.

PP4

Not applicable

PP3

SpliceAI doesn't predict any significant splicing impact (Δ scores ≤ 0.20).

PP2

Not applicable

PP1

No relevant cases found in literature search, including LOVD, HGMD, ClinVar, COSMIC, Mastermind, and Google/Google Scholar searches.

BA1

PM5

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

PM1

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

PM4

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

PM3

Not applicable

PM6

No relevant cases found in literature search, including LOVD, HGMD, ClinVar, COSMIC, Mastermind, and Google/Google Scholar searches.

PM2

PVS1

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

Curation History

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