NM_001754.5(RUNX1):c.490G>A (p.Val164Ile) AND Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 16, 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:: RCV003090339.3

Allele description [Variation Report for NM_001754.5(RUNX1):c.490G>A (p.Val164Ile)]

NM_001754.5(RUNX1):c.490G>A (p.Val164Ile)

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.490G>A (p.Val164Ile)

Other names:

NM_001754.5(RUNX1):c.490G>A; p.Val164Ile

HGVS:

NC_000021.9:g.34880575C>T
NG_011402.2:g.1109137G>A
NM_001001890.3:c.409G>A
NM_001122607.2:c.409G>A
NM_001754.5:c.490G>AMANE SELECT
NP_001001890.1:p.Val137Ile
NP_001116079.1:p.Val137Ile
NP_001745.2:p.Val164Ile
NP_001745.2:p.Val164Ile
LRG_482t1:c.490G>A
LRG_482:g.1109137G>A
LRG_482p1:p.Val164Ile
NC_000021.8:g.36252872C>T
NM_001754.4:c.490G>A

Protein change:

V137I

Molecular consequence:

NM_001001890.3:c.409G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001122607.2:c.409G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001754.5:c.490G>A - 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

Recent activity

Clear Turn Off Turn On

Synthetic construct Homo sapiens clone IMAGE:100016027, MGC:184166 anoctamin 2 (...
Synthetic construct Homo sapiens clone IMAGE:100016027, MGC:184166 anoctamin 2 (ANO2) mRNA, encodes complete protein
gi|157169619|gb|BC152768.1|

Nucleotide

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003479450	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 16, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003479450

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 16, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003479450.2

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

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. 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 affected with RUNX1-related conditions. This variant is present in population databases (rs760221080, gnomAD 0.006%). This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 164 of the RUNX1 protein (p.Val164Ile).

#	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

ClinVar

Relating variation to medicine