NM_000251.3(MSH2):c.913G>A (p.Ala305Thr) AND Hereditary cancer-predisposing syndrome

Germline classification:: Likely benign (3 submissions)
Last evaluated:: Dec 8, 2020
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:: RCV000115547.20

Allele description [Variation Report for NM_000251.3(MSH2):c.913G>A (p.Ala305Thr)]

NM_000251.3(MSH2):c.913G>A (p.Ala305Thr)

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.913G>A (p.Ala305Thr)

Other names:

p.A305T:GCA>ACA

HGVS:

NC_000002.12:g.47414389G>A
NG_007110.2:g.16266G>A
NM_000251.3:c.913G>AMANE SELECT
NM_001258281.1:c.715G>A
NP_000242.1:p.Ala305Thr
NP_000242.1:p.Ala305Thr
NP_001245210.1:p.Ala239Thr
LRG_218t1:c.913G>A
LRG_218:g.16266G>A
LRG_218p1:p.Ala305Thr
NC_000002.11:g.47641528G>A
NM_000251.1:c.913G>A
NM_000251.2:c.913G>A
P43246:p.Ala305Thr
p.A305T

Protein change:

A239T

Links:

UniProtKB: P43246#VAR_004476; dbSNP: rs63751454

NCBI 1000 Genomes Browser:

rs63751454

Molecular consequence:

NM_000251.3:c.913G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001258281.1:c.715G>A - 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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000213040	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely benign (Oct 18, 2018)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 18822302, 19267393, 22102614, 25637381, 9311737 Citation Link,
SCV000537524	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (Sep 19, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002526756	Sema4, Sema4	criteria provided, single submitter (Sema4 Curation Guidelines)	Likely benign (Dec 8, 2020)	germline	curation	PubMed (7) [See all records that cite these PMIDs] 29360161, 27273229, 22102614, 9709044, 9311737, 18822302, 30998989 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000213040

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely benign
(Oct 18, 2018)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Citation Link,

SCV000537524

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely benign
(Sep 19, 2019)

germline

clinical testing

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

SCV002526756

Sema4, Sema4

criteria provided, single submitter

(Sema4 Curation Guidelines)

Likely benign
(Dec 8, 2020)

germline

curation

PubMed (7)
[See all records that cite these PMIDs]

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, curation

Citations

PubMed

Classifying MLH1 and MSH2 variants using bioinformatic prediction, splicing assays, segregation, and tumor characteristics.

Arnold S, Buchanan DD, Barker M, Jaskowski L, Walsh MD, Birney G, Woods MO, Hopper JL, Jenkins MA, Brown MA, Tavtigian SV, Goldgar DE, Young JP, Spurdle AB.

Hum Mutat. 2009 May;30(5):757-70. doi: 10.1002/humu.20936.

PubMed [citation]

PMID:: 19267393
PMCID:: PMC2707453

Actionable exomic incidental findings in 6503 participants: challenges of variant classification.

Amendola LM, Dorschner MO, Robertson PD, Salama JS, Hart R, Shirts BH, Murray ML, Tokita MJ, Gallego CJ, Kim DS, Bennett JT, Crosslin DR, Ranchalis J, Jones KL, Rosenthal EA, Jarvik ER, Itsara A, Turner EH, Herman DS, Schleit J, Burt A, Jamal SM, et al.

Genome Res. 2015 Mar;25(3):305-15. doi: 10.1101/gr.183483.114. Epub 2015 Jan 30.

PubMed [citation]

PMID:: 25637381
PMCID:: PMC4352885

See all PubMed Citations (10)

Details of each submission

From Ambry Genetics, SCV000213040.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

#	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 Color Diagnostics, LLC DBA Color Health, SCV000537524.4

#	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 Sema4, Sema4, SCV002526756.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (7)

#	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: Oct 13, 2024

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