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NM_001754.5(RUNX1):c.500G>C (p.Ser167Thr) AND Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Mar 20, 2021
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:
RCV002044851.6

Allele description [Variation Report for NM_001754.5(RUNX1):c.500G>C (p.Ser167Thr)]

NM_001754.5(RUNX1):c.500G>C (p.Ser167Thr)

Genes:
RUNX1:RUNX family transcription factor 1 [Gene - OMIM - HGNC]
RUNX1-AS1:RUNX1 antisense RNA 1 [Gene - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
21q22.12
Genomic location:
Preferred name:
NM_001754.5(RUNX1):c.500G>C (p.Ser167Thr)
Other names:
NM_001754.5(RUNX1):c.500G>C; p.Ser167Thr
HGVS:
  • NC_000021.9:g.34880565C>G
  • NG_011402.2:g.1109147G>C
  • NM_001001890.3:c.419G>C
  • NM_001122607.2:c.419G>C
  • NM_001754.5:c.500G>CMANE SELECT
  • NP_001001890.1:p.Ser140Thr
  • NP_001116079.1:p.Ser140Thr
  • NP_001745.2:p.Ser167Thr
  • LRG_482:g.1109147G>C
  • NC_000021.8:g.36252862C>G
Protein change:
S140T
Links:
dbSNP: rs2146360406
NCBI 1000 Genomes Browser:
rs2146360406
Molecular consequence:
  • NM_001001890.3:c.419G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001122607.2:c.419G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001754.5:c.500G>C - missense variant - [Sequence Ontology: SO:0001583]

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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002108209Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Mar 20, 2021) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Whole-exome sequencing confirmation of a novel heterozygous mutation in RUNX1 in a pregnant woman with platelet disorder.

Obata M, Tsutsumi S, Makino S, Takahashi K, Watanabe N, Yoshida T, Tamiya G, Kurachi H.

Platelets. 2015;26(4):364-9. doi: 10.3109/09537104.2014.912750. Epub 2014 May 22.

PubMed [citation]
PMID:
24853048

Recurrent CDC25C mutations drive malignant transformation in FPD/AML.

Yoshimi A, Toya T, Kawazu M, Ueno T, Tsukamoto A, Iizuka H, Nakagawa M, Nannya Y, Arai S, Harada H, Usuki K, Hayashi Y, Ito E, Kirito K, Nakajima H, Ichikawa M, Mano H, Kurokawa M.

Nat Commun. 2014 Aug 27;5:4770. doi: 10.1038/ncomms5770.

PubMed [citation]
PMID:
25159113
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002108209.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant disrupts the p.Ser167 amino acid residue in RUNX1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 24853048, 25159113). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with RUNX1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with threonine at codon 167 of the RUNX1 protein (p.Ser167Thr). The serine residue is moderately conserved and there is a small physicochemical difference between serine and threonine.

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

Last Updated: Oct 20, 2024