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.1277_1278insCCCCCCCCCCC (p.Arg427fs)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA1139666837

931873 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 41b15e95-a09a-4f42-97bf-6ddbb6576d89

Approved on: 2024-08-28

Published on: 2024-08-28

HGVS expressions

NM_001754.5:c.1277_1278insCCCCCCCCCCC

NM_001754.5(RUNX1):c.1277_1278insCCCCCCCCCCC (p.Arg427fs)

NC_000021.9:g.34792302_34792303insGGGGGGGGGGG

CM000683.2:g.34792302_34792303insGGGGGGGGGGG

NC_000021.8:g.36164599_36164600insGGGGGGGGGGG

CM000683.1:g.36164599_36164600insGGGGGGGGGGG

NC_000021.7:g.35086469_35086470insGGGGGGGGGGG

NG_011402.2:g.1197411_1197412insCCCCCCCCCCC

ENST00000675419.1:c.1277_1278insCCCCCCCCCCC

ENST00000300305.7:c.1277_1278insCCCCCCCCCCC

ENST00000344691.8:c.1196_1197insCCCCCCCCCCC

ENST00000399240.5:c.1004_1005insCCCCCCCCCCC

ENST00000437180.5:c.1277_1278insCCCCCCCCCCC

ENST00000482318.5:c.*867_*868insCCCCCCCCCCC

NM_001001890.2:c.1196_1197insCCCCCCCCCCC

NM_001754.4:c.1277_1278insCCCCCCCCCCC

NM_001001890.3:c.1196_1197insCCCCCCCCCCC

Likely Pathogenic

PM2_Supporting PVS1_Strong PM5_Supporting

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

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.1277_1278insCCCCCCCCCCC (p.Arg427ProfsTer?) is an insertion that results in a frameshift. This frameshift variant is located downstream of c.98 (PM5_Supporting). It is not predicted to undergo nonsense-mediated decay, and the resulting frameshift affects positions c.780-c.1440 as per VCEP specifications, which are critical for protein function (PVS1_Strong). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_Supporting). In summary, this variant meets criteria to be classified as likely pathogenic. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PVS1_strong, PM2_supporting, PM5_supporting.

PM2_Supporting

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

PVS1_Strong

This variant is not predicted to undergo NMD, and the truncated/altered region is critical for protein function (frameshift (+) c.780-c.1440 as per VCEP specifications) (PVS1_Strong).

PM5_Supporting

This variant is a frameshift variant that is downstream of c.98 (PM5_Supporting).

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.

BS1

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

BS2

This rule is not applicable for MM-VCEP.

BP5

This rule is not applicable for MM-VCEP.

BP7

This variant is not a synonymous or intronic variant.

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.

BP3

This rule is not applicable for MM-VCEP.

BP4

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

BP1

This rule is not applicable for MM-VCEP.

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.

BA1

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

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.

PM1

This variant is not a missense variant.

PM3

This rule is not applicable for MM-VCEP.

PM6

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

Curation History

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