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.289_299delinsCTCCTTCCGCTG (p.Phe97fs)

CA915952644

647118 (ClinVar)

Gene: RUNX1

Condition: hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 2d0a0109-82ce-4d95-b775-93c4312cc6a3

HGVS expressions

NM_001754.5:c.289_299delinsCTCCTTCCGCTG

NM_001754.5(RUNX1):c.289_299delinsCTCCTTCCGCTG (p.Phe97fs)

NC_000021.9:g.34886895_34886905delinsCAGCGGAAGGAG

CM000683.2:g.34886895_34886905delinsCAGCGGAAGGAG

NC_000021.8:g.36259192_36259202delinsCAGCGGAAGGAG

CM000683.1:g.36259192_36259202delinsCAGCGGAAGGAG

NC_000021.7:g.35181062_35181072delinsCAGCGGAAGGAG

NG_011402.2:g.1102807_1102817delinsCTCCTTCCGCTG

ENST00000675419.1:c.289_299delinsCTCCTTCCGCTG

ENST00000300305.7:c.289_299delinsCTCCTTCCGCTG

ENST00000344691.8:c.208_218delinsCTCCTTCCGCTG

ENST00000358356.9:c.208_218delinsCTCCTTCCGCTG

ENST00000399237.6:c.253_263delinsCTCCTTCCGCTG

ENST00000399240.5:c.208_218delinsCTCCTTCCGCTG

ENST00000437180.5:c.289_299delinsCTCCTTCCGCTG

ENST00000455571.5:c.250_260delinsCTCCTTCCGCTG

ENST00000482318.5:c.59-6192_59-6182delinsCTCCTTCCGCTG

NM_001001890.2:c.208_218delinsCTCCTTCCGCTG

NM_001122607.1:c.208_218delinsCTCCTTCCGCTG

NM_001754.4:c.289_299delinsCTCCTTCCGCTG

NM_001001890.3:c.208_218delinsCTCCTTCCGCTG

NM_001122607.2:c.208_218delinsCTCCTTCCGCTG

Pathogenic

PM5_Supporting PVS1 PM2_Supporting

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

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Myeloid Malignancy VCEP

NM_001754.5(RUNX1):c.289_299delinsCTCCTTCCGCTG (p.Phe97fs) is a frameshift variant. The transcript product is predicted to undergo NMD (PVS1). This variant is completely absent from all population databases with at least 20x coverage for RUNX1 in gnomAD v2.1.1 and v3.1.2 (PM2_supporting). This variant was reported in ClinVar in 2018 by Invitae but the affected status of the proband is unknown (Variation ID 647118). This variant is a frameshift change or agreement in splicing predictors (SSF and MES) showing no splicing effects (PM5_Supporting). In summary, this variant meets the 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.

PM5_Supporting

This is a frameshift variants that are downstream of c.98 (in transcript NM_001754.4)

PVS1

The transcript product of this frameshift variant is predicted to undergo NMD.

PM2_Supporting

This variant is completely absent from all population databases with at least 20x coverage for RUNX1 (PM2_supporting).

BS2

This rule is not applicable for MM-VCEP

BS4

This rule is not applicable because there is no information on segregation in affected individuals with this variant.

BS3

This rule does not apply because there are no functional studies for this variant.

BS1

This rule is not applicable because the variant is completely absent from all population databases.

BP2

This rule is not applicable because we have no phase information in affected individuals for this variant.

BP3

This rule is not applicable for MM-VCEP

BP4

This rule is not applicable because this is a loss of function variant.

BP1

This rule is not applicable for MM-VCEP

BP7

This rule is not applicable because this is a loss of function variant.

BP5

This rule is not applicable for MM-VCEP.

PS2

This rule is not applicable because there are no affected individuals with this variant.

PS4

This rule is not applicable because there is no published information on affected individuals nor a RUNX1 case control study. This variant was reported in ClinVar in 2018 by Invitae but the affected status of the proband is unknown (Variation ID 647118).

PS3

This rule does not apply because there are no functional studies for this variant.

PS1

This rule is not applicable because this is a loss of function variant.

BA1

This rule is not applicable because the variant is completely absent from all population databases.

PP1

This rule is not applicable because there is no information on segregation in affected individuals with this variant.

PP4

This rule is not applicable for MM-VCEP.

PP3

This rule is not applicable because this is a loss of function variant.

PP2

This rule is not applicable for MM-VCEP

PM1

This is a frameshift variant

PM3

This rule is not applicable for MM-VCEP.

PM4

This rule is not applicable because this is a loss of function variant.

PM6

This rule is not applicable because there is no information on affected individuals nor the family.

Approved on: 2023-12-09

Published on: 2023-12-09

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