NM_000251.3(MSH2):c.51C>A (p.Val17=) AND Hereditary cancer-predisposing syndrome

Clinical significance:Conflicting interpretations of pathogenicity, Likely benign(1);Uncertain significance(1) (Last evaluated: Mar 19, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:

Allele description [Variation Report for NM_000251.3(MSH2):c.51C>A (p.Val17=)]

NM_000251.3(MSH2):c.51C>A (p.Val17=)

MSH2:mutS homolog 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_000251.3(MSH2):c.51C>A (p.Val17=)
  • NC_000002.12:g.47403242C>A
  • NG_007110.2:g.5119C>A
  • NM_000251.3:c.51C>AMANE SELECT
  • NM_001258281.1:c.-31+67C>A
  • NP_000242.1:p.Val17=
  • NP_000242.1:p.Val17=
  • LRG_218t1:c.51C>A
  • LRG_218:g.5119C>A
  • LRG_218p1:p.Val17=
  • NC_000002.11:g.47630381C>A
  • NM_000251.1:c.51C>A
  • NM_000251.2:c.51C>A
  • p.V17V
dbSNP: rs397515879
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_001258281.1:c.-31+67C>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000251.3:c.51C>A - synonymous variant - [Sequence Ontology: SO:0001819]


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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000216541Ambry Geneticscriteria provided, single submitter
Uncertain significance
(Mar 19, 2020)
germlineclinical testing

Citation Link,

SCV001349268Color Health, Inccriteria provided, single submitter
Likely benign
(Nov 26, 2018)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing



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]

Details of each submission

From Ambry Genetics, SCV000216541.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided


The c.51C>A variant (also known as p.V17V), located in coding exon 1 of the MSH2 gene, results from a C to A substitution at nucleotide position 51. This nucleotide substitution does not change the at codon 17. However, this change occurs in the base pair of coding exon 1, which makes it likely to have some effect on normal mRNA splicing. This nucleotide position is not well conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to create a new alternate splice donor site; however, it is not predicted to be stronger than the native splice donor site. RNA studies have demonstrated that this alteration results in abnormal splicing in the set of samples tested (Ambry internal data). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

From Color Health, Inc, SCV001349268.1

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

Last Updated: Dec 4, 2021

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