NM_000179.3(MSH6):c.665A>G (p.Asp222Gly) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Oct 5, 2018
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001190342.4

Allele description [Variation Report for NM_000179.3(MSH6):c.665A>G (p.Asp222Gly)]

NM_000179.3(MSH6):c.665A>G (p.Asp222Gly)

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.665A>G (p.Asp222Gly)

HGVS:

NC_000002.12:g.47798648A>G
NG_007111.1:g.20502A>G
NM_000179.3:c.665A>GMANE SELECT
NM_001281492.2:c.275A>G
NM_001281493.2:c.-242A>G
NM_001281494.2:c.-242A>G
NP_000170.1:p.Asp222Gly
NP_001268421.1:p.Asp92Gly
LRG_219t1:c.665A>G
LRG_219:g.20502A>G
NC_000002.11:g.48025787A>G
NM_000179.2:c.665A>G

Protein change:

D222G

Links:

dbSNP: rs750827951

NCBI 1000 Genomes Browser:

rs750827951

Molecular consequence:

NM_001281493.2:c.-242A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001281494.2:c.-242A>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000179.3:c.665A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001281492.2:c.275A>G - 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

Recent activity

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wolframin [Rattus norvegicus]
wolframin [Rattus norvegicus]
gi|13929176|ref|NP_114011.1|

Protein
RecName: Full=Protocadherin beta-1; Short=PCDH-beta-1; Flags: Precursor
RecName: Full=Protocadherin beta-1; Short=PCDH-beta-1; Flags: Precursor
gi|205371811|sp|Q9Y5F3.2|PCDB1_HUMA

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001357802	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Oct 5, 2018)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002661669	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Nov 8, 2017)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001357802

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Oct 5, 2018)

germline

clinical testing

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

SCV002661669

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Nov 8, 2017)

germline

clinical testing

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

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

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV001357802.1

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

#	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

From Ambry Genetics, SCV002661669.2

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

Description

The p.D222G variant (also known as c.665A>G), located in coding exon 4 of the MSH6 gene, results from an A to G substitution at nucleotide position 665. The aspartic acid at codon 222 is replaced by glycine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. In addition, the CoDP in silico tool predicts this alteration to have a minor impact on molecular function, with a score of 0.000 (Terui H et al. J. Biomed. Sci. 2013 Apr;20:25). 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: May 1, 2024

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