NM_000251.3(MSH2):c.336C>A (p.Ser112=) AND Lynch syndrome I

Clinical significance:Conflicting interpretations of pathogenicity, Likely benign(1);Uncertain significance(1) (Last evaluated: Jan 12, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000662370.2

Allele description [Variation Report for NM_000251.3(MSH2):c.336C>A (p.Ser112=)]

NM_000251.3(MSH2):c.336C>A (p.Ser112=)

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.336C>A (p.Ser112=)
HGVS:
  • NC_000002.12:g.47408525C>A
  • NG_007110.2:g.10402C>A
  • NM_000251.2:c.336C>A
  • NM_000251.3:c.336C>AMANE SELECT
  • NM_001258281.1:c.138C>A
  • NP_000242.1:p.Ser112=
  • NP_000242.1:p.Ser112=
  • NP_001245210.1:p.Ser46=
  • LRG_218t1:c.336C>A
  • LRG_218:g.10402C>A
  • LRG_218p1:p.Ser112=
  • NC_000002.11:g.47635664C>A
  • NM_000251.1:c.336C>A
  • p.S112S
  • p.Ser112Ser
Links:
dbSNP: rs34312619
NCBI 1000 Genomes Browser:
rs34312619
Molecular consequence:
  • NM_000251.2:c.336C>A - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_000251.3:c.336C>A - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001258281.1:c.138C>A - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Name:
Lynch syndrome I (COCA1)
Synonyms:
COLON CANCER, FAMILIAL NONPOLYPOSIS, TYPE 1; MSH2-Related Hereditary Non-Polyposis Colon Cancer; Lynch syndrome 1; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0007356; MedGen: C2936783; Orphanet: 144; OMIM: 120435

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000430912Illumina Clinical Services Laboratory,Illuminacriteria provided, single submitter
Uncertain significance
(Jan 12, 2018)
germlineclinical testing

Citation Link,

SCV000784762Counsylcriteria provided, single submitter
Likely benign
(Nov 13, 2017)
unknownclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Counsyl_Autosomal_Dominant_Disease_Classification_criteria_(2015)_v1.pdf

Citation Link

Summary from all submissions

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

Citations

PubMed

Screening for the Lynch syndrome (hereditary nonpolyposis colorectal cancer).

Hampel H, Frankel WL, Martin E, Arnold M, Khanduja K, Kuebler P, Nakagawa H, Sotamaa K, Prior TW, Westman J, Panescu J, Fix D, Lockman J, Comeras I, de la Chapelle A.

N Engl J Med. 2005 May 5;352(18):1851-60.

PubMed [citation]
PMID:
15872200

RBP-Var: a database of functional variants involved in regulation mediated by RNA-binding proteins.

Mao F, Xiao L, Li X, Liang J, Teng H, Cai W, Sun ZS.

Nucleic Acids Res. 2016 Jan 4;44(D1):D154-63. doi: 10.1093/nar/gkv1308. Epub 2015 Dec 3.

PubMed [citation]
PMID:
26635394
PMCID:
PMC4702914

Details of each submission

From Illumina Clinical Services Laboratory,Illumina, SCV000430912.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.

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

From Counsyl, SCV000784762.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 27, 2021

Support Center