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NM_001754.5(RUNX1):c.165dup (p.Leu56fs) AND Hereditary thrombocytopenia and hematologic cancer predisposition syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Mar 26, 2024
Review status:
3 stars out of maximum of 4 stars
reviewed by expert panel
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV003448392.2

Allele description [Variation Report for NM_001754.5(RUNX1):c.165dup (p.Leu56fs)]

NM_001754.5(RUNX1):c.165dup (p.Leu56fs)

Gene:
RUNX1:RUNX family transcription factor 1 [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
21q22.12
Genomic location:
Preferred name:
NM_001754.5(RUNX1):c.165dup (p.Leu56fs)
Other names:
NM_001754.5(RUNX1):c.165dup; p.Leu56fs
HGVS:
  • NC_000021.9:g.34887029dup
  • NG_011402.2:g.1102683dup
  • NM_001001890.3:c.84dup
  • NM_001122607.2:c.84dup
  • NM_001754.5:c.165dupMANE SELECT
  • NP_001001890.1:p.Leu29fs
  • NP_001116079.1:p.Leu29fs
  • NP_001745.2:p.Leu56fs
  • LRG_482:g.1102683dup
  • NC_000021.8:g.36259326dup
  • NM_001754.5:c.164_165insGMANE SELECT
Protein change:
L29fs
Links:
dbSNP: rs2058004321
NCBI 1000 Genomes Browser:
rs2058004321
Molecular consequence:
  • NM_001001890.3:c.84dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001122607.2:c.84dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001754.5:c.165dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Hereditary thrombocytopenia and hematologic cancer predisposition syndrome
Identifiers:
MONDO: MONDO:0011071; MedGen: CN281654

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004176238ClinGen Myeloid Malignancy Variant Curation Expert Panel
reviewed by expert panel

(ClinGen MyeloMalig ACMG Specifications v2)		Pathogenic
(Mar 26, 2024) 		germlinecuration

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration

Details of each submission

From ClinGen Myeloid Malignancy Variant Curation Expert Panel, SCV004176238.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

NM_001754.5(RUNX1):c.165dup (p.Leu56ValfsTer?) is a duplication frameshift variant which results in a termination sequence 82 residues later. 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). 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 (PM5_Supporting). This variant has been reported in one proband meeting at least one of the RUNX1-phenotypic criteria (PS4_ Supporting; PMID: 18723428). 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, PM5_supporting, PM2_supporting, PS4_supporting.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jul 29, 2024