NM_001754.5(RUNX1):c.166_193dup (p.Ala65fs) AND Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 17, 2018
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV000692523.6

Allele description [Variation Report for NM_001754.5(RUNX1):c.166_193dup (p.Ala65fs)]

NM_001754.5(RUNX1):c.166_193dup (p.Ala65fs)

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.166_193dup (p.Ala65fs)

Other names:

NM_001754.5(RUNX1):c.166_193dup; p.Ala65fs

HGVS:

NC_000021.9:g.34887005_34887032dup
NG_011402.2:g.1102684_1102711dup
NM_001001890.3:c.85_112dup
NM_001122607.2:c.85_112dup
NM_001754.5:c.166_193dupMANE SELECT
NP_001001890.1:p.Ala38fs
NP_001116079.1:p.Ala38fs
NP_001745.2:p.Ala65fs
NP_001745.2:p.Ala65fs
LRG_482t1:c.166_193dup
LRG_482:g.1102684_1102711dup
LRG_482p1:p.Ala65fs
NC_000021.8:g.36259297_36259298insCGCCGGCGTCCGGGGCGCCCAGCGGCAA
NC_000021.8:g.36259302_36259329dup
NM_001754.4:c.166_193dup

Protein change:

A38fs

Links:

dbSNP: rs1569084530

NCBI 1000 Genomes Browser:

rs1569084530

Molecular consequence:

NM_001001890.3:c.85_112dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001122607.2:c.85_112dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001754.5:c.166_193dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1
Synonyms:: Platelet disorder, Aspirin-like; Familial platelet disorder with associated myeloid malignancy; Familial Platelet Disorder with Propensity to Acute Myelogenous Leukemia; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0100083; MeSH: C563324; MedGen: C1832388; Orphanet: 71290; OMIM: 601399

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PDE1C phosphodiesterase 1C [Homo sapiens]
PDE1C phosphodiesterase 1C [Homo sapiens]
Gene ID:5137

Gene
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Profile neighbors for GEO Profiles (Select 22830029) (11)
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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000820350	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 17, 2018)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 18723428, 24100448, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000820350

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 17, 2018)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Five new pedigrees with inherited RUNX1 mutations causing familial platelet disorder with propensity to myeloid malignancy.

Owen CJ, Toze CL, Koochin A, Forrest DL, Smith CA, Stevens JM, Jackson SC, Poon MC, Sinclair GD, Leber B, Johnson PR, Macheta A, Yin JA, Barnett MJ, Lister TA, Fitzgibbon J.

Blood. 2008 Dec 1;112(12):4639-45. doi: 10.1182/blood-2008-05-156745. Epub 2008 Aug 21.

PubMed [citation]

PMID:: 18723428

Enrichment of FLI1 and RUNX1 mutations in families with excessive bleeding and platelet dense granule secretion defects.

Stockley J, Morgan NV, Bem D, Lowe GC, Lordkipanidzé M, Dawood B, Simpson MA, Macfarlane K, Horner K, Leo VC, Talks K, Motwani J, Wilde JT, Collins PW, Makris M, Watson SP, Daly ME; UK Genotyping and Phenotyping of Platelets Study Group..

Blood. 2013 Dec 12;122(25):4090-3. doi: 10.1182/blood-2013-06-506873. Epub 2013 Oct 7.

PubMed [citation]

PMID:: 24100448
PMCID:: PMC3862284

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000820350.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in RUNX1 are known to be pathogenic (PMID: 18723428, 24100448). This variant has not been reported in the literature in individuals with RUNX1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Ala65Valfs*82) in the RUNX1 gene. It is expected to result in an absent or disrupted protein product.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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