NM_001754.5(RUNX1):c.351+2T>A AND Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 28, 2022
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:: RCV001213758.6

Allele description [Variation Report for NM_001754.5(RUNX1):c.351+2T>A]

NM_001754.5(RUNX1):c.351+2T>A

Gene:

RUNX1:RUNX family transcription factor 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

21q22.12

Genomic location:

Preferred name:

NM_001754.5(RUNX1):c.351+2T>A

HGVS:

NC_000021.9:g.34886841A>T
NG_011402.2:g.1102871T>A
NG_144242.1:g.316A>T
NM_001001890.3:c.270+2T>A
NM_001122607.2:c.270+2T>A
NM_001754.5:c.351+2T>AMANE SELECT
LRG_482t1:c.351+2T>A
LRG_482:g.1102871T>A
NC_000021.8:g.36259138A>T
NM_001754.4:c.351+2T>A

Links:

dbSNP: rs2057997150

NCBI 1000 Genomes Browser:

rs2057997150

Molecular consequence:

NM_001001890.3:c.270+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001122607.2:c.270+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001754.5:c.351+2T>A - splice donor variant - [Sequence Ontology: SO:0001575]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001385407	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 28, 2022)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 27931139, 28240786, 16199547, 18723428, 24100448, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001385407

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 28, 2022)

germline

clinical testing

PubMed (6)
[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

Clinical characteristics and platelet phenotype in a family with RUNX1 mutated thrombocytopenia.

Perez Botero J, Chen D, Cousin MA, Majerus JA, Coon LM, Kruisselbrink TM, Klee EW, Lazaridis KN, Pruthi RK, Patnaik MM.

Leuk Lymphoma. 2017 Aug;58(8):1963-1967. doi: 10.1080/10428194.2016.1265118. Epub 2016 Dec 8. No abstract available.

PubMed [citation]

PMID:: 27931139

Mutations of RUNX1 in families with inherited thrombocytopenia.

De Rocco D, Melazzini F, Marconi C, Pecci A, Bottega R, Gnan C, Palombo F, Giordano P, Coccioli MS, Glembotsky AC, Heller PG, Seri M, Savoia A, Noris P.

Am J Hematol. 2017 Jun;92(6):E86-E88. doi: 10.1002/ajh.24703. Epub 2017 Mar 24. No abstract available.

PubMed [citation]

PMID:: 28240786

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001385407.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 943551). Disruption of this splice site has been observed in individual(s) with clinical features of RUNX1-related conditions (PMID: 27931139, 28240786). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 4 of the RUNX1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in RUNX1 are known to be pathogenic (PMID: 18723428, 24100448).

#	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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