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.204C>G (p.Ala68=)

CA10014570

762564 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 7b392d3c-4505-4e91-bfad-ec25756afeed

HGVS expressions

NM_001754.5:c.204C>G

NM_001754.5(RUNX1):c.204C>G (p.Ala68=)

NC_000021.9:g.34886990G>C

CM000683.2:g.34886990G>C

NC_000021.8:g.36259287G>C

CM000683.1:g.36259287G>C

NC_000021.7:g.35181157G>C

NG_011402.2:g.1102722C>G

ENST00000675419.1:c.204C>G

ENST00000300305.7:c.204C>G

ENST00000344691.8:c.123C>G

ENST00000358356.9:c.123C>G

ENST00000399237.6:c.168C>G

ENST00000399240.5:c.123C>G

ENST00000437180.5:c.204C>G

ENST00000455571.5:c.165C>G

ENST00000482318.5:c.59-6277C>G

NM_001001890.2:c.123C>G

NM_001122607.1:c.123C>G

NM_001754.4:c.204C>G

NM_001001890.3:c.123C>G

NM_001122607.2:c.123C>G

Likely Benign

BS1 BP4 BP7

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

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.204C>G (p.Ala68=) is a synonymous variant which has a MAF of 0.00017 (0.017%, 5/30230, 30235 alleles) in the South Asian subpopulation of the gnomAD v2 cohort is between 0.00015 (0.015%) and 0.0015 (0.15%) (BS1). This is a synonymous variant, therefore REVEL is not calculable. On the basis of SpliceAI, the predicted effects on splicing are: Acceptor loss 0.00, donor loss 0.00, acceptor gain 0.00, donor gain 0.00. Therefore, there is no computationally predicted effect on splicing (BP4). On the basis of SpliceAI, the predicted effects on splicing are: Acceptor loss 0.00, donor loss 0.00, acceptor gain 0.00, donor gain 0.00. Therefore, there is no computationally predicted effect on splicing. Evolutionary conservation prediction algorithms predict the site as not being conserved (PhyloP score 1.84737 < 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 likely benign. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BS1, BP4, BP7.

BS1

MAF of 0.00017 (0.017%, 5/30230, 30235 alleles) in the South Asian subpopulation of the gnomAD v2 cohort is between 0.00015 (0.015%) and 0.0015 (0.15%) (BS1 is met). Note: The variant is classified as likely benign based on BS1 alone with no contradictory evidence supporting pathogenicity.

BP4

This is a synonymous variant, therefore REVEL is not calculable. On the basis of SpliceAI, the predicted effects on splicing are: Acceptor loss 0.00, donor loss 0.00, acceptor gain 0.00, donor gain 0.00. Therefore, there is no computationally predicted effect on splicing. (BP4 IS MET)

BP7

On the basis of SpliceAI, the predicted effects on splicing are: Acceptor loss 0.00, donor loss 0.00, acceptor gain 0.00, donor gain 0.00. Therefore, there is no computationally predicted effect on splicing. Evolutionary conservation prediction algorithms predict the site as not being conserved (PhyloP score 1.84737 < 2.0 or the variant is the reference nucleotide in one primate and/or three mammal species) (BP7 IS MET).

PS2

A comprehensive search of multiple resources (PubMed, Google Scholar, etc.) revealed no publications with this specific variant.

PS4

A comprehensive search of multiple resources (PubMed, Google Scholar, etc.) revealed no publications with this specific variant.

PS3

A comprehensive search of multiple resources (PubMed, Google Scholar, etc.) revealed no publications with this specific variant.

PS1

This is a synonymous variant, therefore PS1 is NOT MET.

BA1

BA1 is NOT MET

PP1

A comprehensive search of multiple resources (PubMed, Google Scholar, etc.) revealed no publications with this specific variant.

PP4

This rule is not applicable for MM-VCEP

PP3

PP2

This rule is not applicable for MM-VCEP

PM1

This variant occurs outside the conserved Runt Homology Domain of RUNX1 (AA 89-204).

PM5

This is a synonymous variant, therefore PM5 is NOT MET.

PM3

This rule is not applicable for MM-VCEP

PM4

This is a synonymous variant, therefore PM4 is NOT MET.

PM6

A comprehensive search of multiple resources (PubMed, Google Scholar, etc.) revealed no publications with this specific variant.

PM2

PM2 is NOT MET

PVS1

This is a synonymous variant, therefore PVS1 is NOT MET.

BS2

This rule is not applicable for MM-VCEP

BS4

A comprehensive search of multiple resources (PubMed, Google Scholar, etc.) revealed no publications with this specific variant.

BS3

A comprehensive search of multiple resources (PubMed, Google Scholar, etc.) revealed no publications with this specific variant.

BP2

A comprehensive search of multiple resources (PubMed, Google Scholar, etc.) revealed no publications with this specific variant.

BP3

This rule is not applicable for MM-VCEP

BP1

This rule is not applicable for MM-VCEP

BP5

This rule is not applicable for MM-VCEP

Approved on: 2024-06-24

Published on: 2024-06-24

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