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.247dup (p.Ala83fs)

CA2499225883

1073907 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: a17cc2cb-3b5c-4d98-8710-4f50cc98af79

HGVS expressions

NM_001754.5:c.247dup

NM_001754.5(RUNX1):c.247dup (p.Ala83fs)

NC_000021.9:g.34886948dup

CM000683.2:g.34886948dup

NC_000021.8:g.36259245dup

CM000683.1:g.36259245dup

NC_000021.7:g.35181115dup

NG_011402.2:g.1102765dup

ENST00000675419.1:c.247dup

ENST00000300305.7:c.247dup

ENST00000344691.8:c.166dup

ENST00000358356.9:c.166dup

ENST00000399237.6:c.211dup

ENST00000399240.5:c.166dup

ENST00000437180.5:c.247dup

ENST00000455571.5:c.208dup

ENST00000482318.5:c.59-6234dup

NM_001001890.2:c.166dup

NM_001122607.1:c.166dup

NM_001754.4:c.247dup

NM_001001890.3:c.166dup

NM_001122607.2:c.166dup

Pathogenic

PVS1 PM2_Supporting PM5_Supporting

PS2 PS4 PS3 PS1 PM1 PM4 PM3 PM6 BA1 BP3 BP2 BP4 BP1 BP7 BP5 BS2 BS1 BS4 BS3 PP1 PP4 PP3 PP2

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

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Myeloid Malignancy VCEP

NM_001754.5(RUNX1):c.247dup (p.Ala83GlyfsTer?) is an insertion frameshift variant which results in a termination sequence 55 residues later. This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_Supporting). This variant is a nonsense/frameshift variants that is downstream of c.98. This variant is predicted to undergo nonsense mediated decay in a gene in which loss-of-function is an established mechanism (frameshift (+) c.98-c.779 as per VCEP specifications) (PVS1). In summary, this variant meets criteria to be classified as pathogenic. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PVS1, PM2_supporting, PM5_supporting.

PVS1

This variant is predicted to undergo nonsense mediated decay in a gene in which loss-of-function is an established mechanism (frameshift (+) c.98-c.779 as per VCEP specifications) (PVS1).

PM2_Supporting

This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_Supporting).

PM5_Supporting

This variant is a nonsense/frameshift variants that is downstream of c.98.

PS2

De novo data for this variant has not been reported in literature.

PS4

Proband data for this variant has not been reported in literature.

PS3

In vitro or in vivo functional data has not been reported for this variant in the literature.

PS1

There has not yet been a missense change determined to be pathogenic at this amino acid residue.

PM1

This variant does not affect any of the following amino acid residues, nor is it located within the RHD: R107, K110, A134, R162, R166, S167, R169, G170, K194, T196, D198, R201, R204 OR within residues 89-204.

PM4

This variant is not an in-frame deletion/insertion.

PM3

This rule is not applicable for MM-VCEP.

PM6

De novo data for this variant has not been reported in literature.

BA1

This variant does not have a MAF ≥ 0.0015 (0.15%) in any general continental population dataset.

BP3

This rule is not applicable for MM-VCEP.

BP2

This variant has not been observed in trans with a pathogenic variant for a fully penetrant dominant gene/disorder or observed in cis with a pathogenic variant in any inheritance pattern.

BP4

This variant does not have applicable in-silico data available.

BP1

This rule is not applicable for MM-VCEP.

BP7

This variant is not a synonymous or intronic variant.

BP5

This rule is not applicable for MM-VCEP.

BS2

This rule is not applicable for MM-VCEP.

BS1

This variant does not have a MAF between 0.00015 (0.015%) and 0.0015 (0.15%) in any general continental dataset.

BS4

Segregation data for this variant has not been reported in literature.

BS3

In vitro or in vivo functional data has not been reported for this variant in the literature.

PP1

Segregation data for this variant has not been reported in literature.

PP4

This rule is not applicable for MM-VCEP.

PP3

This variant does not have applicable in-silico data available.

PP2

This rule is not applicable for MM-VCEP.

Approved on: 2023-12-09

Published on: 2023-12-09

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