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NM_000179.3(MSH6):c.663A>C (p.Glu221Asp) AND Lynch syndrome 5

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
May 1, 2019
Review status:
criteria provided, conflicting classifications
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:
RCV000659887.17

Allele description [Variation Report for NM_000179.3(MSH6):c.663A>C (p.Glu221Asp)]

NM_000179.3(MSH6):c.663A>C (p.Glu221Asp)

Gene:
MSH6:mutS homolog 6 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2p16.3
Genomic location:
Preferred name:
NM_000179.3(MSH6):c.663A>C (p.Glu221Asp)
Other names:
p.E221D:GAA>GAC
HGVS:
  • NC_000002.12:g.47798646A>C
  • NG_007111.1:g.20500A>C
  • NM_000179.3:c.663A>CMANE SELECT
  • NM_001281492.2:c.273A>C
  • NM_001281493.2:c.-244A>C
  • NM_001281494.2:c.-244A>C
  • NP_000170.1:p.Glu221Asp
  • NP_000170.1:p.Glu221Asp
  • NP_001268421.1:p.Glu91Asp
  • LRG_219t1:c.663A>C
  • LRG_219:g.20500A>C
  • LRG_219p1:p.Glu221Asp
  • NC_000002.11:g.48025785A>C
  • NM_000179.2:c.663A>C
  • P52701:p.Glu221Asp
  • p.E221D
Protein change:
E221D
Links:
UniProtKB: P52701#VAR_042274; dbSNP: rs41557217
NCBI 1000 Genomes Browser:
rs41557217
Molecular consequence:
  • NM_001281493.2:c.-244A>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001281494.2:c.-244A>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_000179.3:c.663A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001281492.2:c.273A>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Lynch syndrome 5 (LYNCH5)
Synonyms:
Colorectal cancer, hereditary nonpolyposis, type 5; Hereditary non-polyposis colorectal cancer, type 5
Identifiers:
MONDO: MONDO:0013710; MedGen: C1833477; Orphanet: 144; OMIM: 614350

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000781782Center for Human Genetics, Inc, Center for Human Genetics, Inc
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Nov 1, 2016) 		germlineclinical testing

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

SCV001302617Illumina Laboratory Services, Illumina
criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)		Uncertain significance
(May 1, 2019) 		germlineclinical testing

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

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Germline MSH6 mutations are more prevalent in endometrial cancer patient cohorts than hereditary non polyposis colorectal cancer cohorts.

Devlin LA, Graham CA, Price JH, Morrison PJ.

Ulster Med J. 2008 Jan;77(1):25-30.

PubMed [citation]
PMID:
18269114
PMCID:
PMC2397009

Details of each submission

From Center for Human Genetics, Inc, Center for Human Genetics, Inc, SCV000781782.1

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

From Illumina Laboratory Services, Illumina, SCV001302617.1

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

Description

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

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

Last Updated: Oct 8, 2024