NM_000251.3(MSH2):c.2272G>A (p.Asp758Asn) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 4, 2020
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:: RCV002446812.2

Allele description [Variation Report for NM_000251.3(MSH2):c.2272G>A (p.Asp758Asn)]

NM_000251.3(MSH2):c.2272G>A (p.Asp758Asn)

Gene:

MSH2:mutS homolog 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2p21

Genomic location:

Preferred name:

NM_000251.3(MSH2):c.2272G>A (p.Asp758Asn)

HGVS:

NC_000002.12:g.47478333G>A
NG_007110.2:g.80210G>A
NM_000251.3:c.2272G>AMANE SELECT
NM_001258281.1:c.2074G>A
NP_000242.1:p.Asp758Asn
NP_000242.1:p.Asp758Asn
NP_001245210.1:p.Asp692Asn
LRG_218t1:c.2272G>A
LRG_218:g.80210G>A
LRG_218p1:p.Asp758Asn
NC_000002.11:g.47705472G>A
NM_000251.1:c.2272G>A
NM_000251.2:c.2272G>A

Protein change:

D692N

Links:

dbSNP: rs876658254

NCBI 1000 Genomes Browser:

rs876658254

Molecular consequence:

NM_000251.3:c.2272G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001258281.1:c.2074G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002733286	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Aug 4, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002733286

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Aug 4, 2020)

germline

clinical testing

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

Citation Link

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

Targeted Next-Generation Sequencing of MLH1, MSH2, and MSH6 Genes in Patients with Endometrial Carcinoma under 50 Years of Age

Özdemir TR, Alan M, Sancı M, Koç A.

Balkan Med J. 2019 Jan 1;36(1):37-42. doi: 10.4274/balkanmedj.2018.0922. Epub 2018 Sep 21.

PubMed [citation]

PMID:: 30238922
PMCID:: PMC6335935

Details of each submission

From Ambry Genetics, SCV002733286.2

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

Description

The p.D758N variant (also known as c.2272G>A), located in coding exon 14 of the MSH2 gene, results from a G to A substitution at nucleotide position 2272. The aspartic acid at codon 758 is replaced by asparagine, an amino acid with highly similar properties. This alteration was identified in a patient with endometrial cancer diagnosed at age 41 with a family history of colorectal cancer in their father at age 80 (Özdemir TR et al. Balkan Med J, 2019 01;36:37-42). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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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