NM_000251.3(MSH2):c.1962C>G (p.Asp654Glu) AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 9, 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:: RCV001240753.7

Allele description [Variation Report for NM_000251.3(MSH2):c.1962C>G (p.Asp654Glu)]

NM_000251.3(MSH2):c.1962C>G (p.Asp654Glu)

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.1962C>G (p.Asp654Glu)

HGVS:

NC_000002.12:g.47475227C>G
NG_007110.2:g.77104C>G
NM_000251.3:c.1962C>GMANE SELECT
NM_001258281.1:c.1764C>G
NP_000242.1:p.Asp654Glu
NP_000242.1:p.Asp654Glu
NP_001245210.1:p.Asp588Glu
LRG_218t1:c.1962C>G
LRG_218:g.77104C>G
LRG_218p1:p.Asp654Glu
NC_000002.11:g.47702366C>G
NM_000251.1:c.1962C>G
NM_000251.2:c.1962C>G

Protein change:

D588E

Links:

dbSNP: rs751939698

NCBI 1000 Genomes Browser:

rs751939698

Molecular consequence:

NM_000251.3:c.1962C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001258281.1:c.1764C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary nonpolyposis colorectal neoplasms
Identifiers:: MeSH: D003123; MedGen: C0009405

Recent activity

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Homo sapiens cubilin (intrinsic factor-cobalamin receptor) (CUBN), mRNA
Homo sapiens cubilin (intrinsic factor-cobalamin receptor) (CUBN), mRNA
gi|4557502|ref|NM_001081.1|

Nucleotide
thop1 thimet oligopeptidase 1 [Danio rerio]
thop1 thimet oligopeptidase 1 [Danio rerio]
Gene ID:436628

Gene
snx17 sorting nexin 17 [Danio rerio]
snx17 sorting nexin 17 [Danio rerio]
Gene ID:568263

Gene
cmpk cytidylate kinase [Danio rerio]
cmpk cytidylate kinase [Danio rerio]
Gene ID:406383

Gene
dpysl5a dihydropyrimidinase like 5a [Danio rerio]
dpysl5a dihydropyrimidinase like 5a [Danio rerio]
Gene ID:324416

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001413723	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 9, 2020)	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

SCV001413723

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 9, 2020)

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, SCV001413723.5

#	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 with MSH2-related conditions. ClinVar contains an entry for this variant (Variation ID: 231656). This variant is not present in population databases (ExAC no frequency). This sequence change replaces aspartic acid with glutamic acid at codon 654 of the MSH2 protein (p.Asp654Glu). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and glutamic acid.

#	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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