NM_000251.3(MSH2):c.1139T>C (p.Leu380Ser) AND Hereditary cancer-predisposing syndrome

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Sep 8, 2023
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:: RCV000215764.7

Allele description [Variation Report for NM_000251.3(MSH2):c.1139T>C (p.Leu380Ser)]

NM_000251.3(MSH2):c.1139T>C (p.Leu380Ser)

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.1139T>C (p.Leu380Ser)

Other names:

p.L380S:TTA>TCA

HGVS:

NC_000002.12:g.47429804T>C
NG_007110.2:g.31681T>C
NM_000251.3:c.1139T>CMANE SELECT
NM_001258281.1:c.941T>C
NP_000242.1:p.Leu380Ser
NP_000242.1:p.Leu380Ser
NP_001245210.1:p.Leu314Ser
LRG_218t1:c.1139T>C
LRG_218:g.31681T>C
LRG_218p1:p.Leu380Ser
NC_000002.11:g.47656943T>C
NM_000251.1:c.1139T>C
NM_000251.2:c.1139T>C

Protein change:

L314S

Links:

dbSNP: rs730881755

NCBI 1000 Genomes Browser:

rs730881755

Molecular consequence:

NM_000251.3:c.1139T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001258281.1:c.941T>C - 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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PREDICTED: Pteronotus mesoamericanus aspartate beta-hydroxylase (ASPH), transcri...
PREDICTED: Pteronotus mesoamericanus aspartate beta-hydroxylase (ASPH), transcript variant X14, mRNA
gi|2466549950|ref|XM_054590182.1|

Nucleotide
aspartyl/asparaginyl beta-hydroxylase isoform X9 [Pteronotus mesoamericanus]
aspartyl/asparaginyl beta-hydroxylase isoform X9 [Pteronotus mesoamericanus]
gi|2466549939|ref|XP_054446152.1|

Protein
rab GDP dissociation inhibitor beta isoform 2 [Homo sapiens]
rab GDP dissociation inhibitor beta isoform 2 [Homo sapiens]
gi|169646441|ref|NP_001108628.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000275173	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely benign (Sep 8, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29439113, 33357406 Citation Link,
SCV002528814	Sema4, Sema4	criteria provided, single submitter (Sema4 Curation Guidelines)	Uncertain significance (Dec 28, 2021)	germline	curation	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000275173

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely benign
(Sep 8, 2023)

germline

clinical testing

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

Citation Link,

SCV002528814

Sema4, Sema4

criteria provided, single submitter

(Sema4 Curation Guidelines)

Uncertain significance
(Dec 28, 2021)

germline

curation

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

Double somatic mutations in mismatch repair genes are frequent in colorectal cancer after Hodgkin's lymphoma treatment.

Rigter LS, Snaebjornsson P, Rosenberg EH, Atmodimedjo PN, Aleman BM, Ten Hoeve J, Geurts-Giele WR; PALGA group., van Ravesteyn TW, Hoeksel J, Meijer GA, Te Riele H, van Leeuwen FE, Dinjens WN, van Leerdam ME.

Gut. 2018 Mar;67(3):447-455. doi: 10.1136/gutjnl-2016-312608. Epub 2016 Nov 8.

PubMed [citation]

PMID:: 29439113

Massively parallel functional testing of MSH2 missense variants conferring Lynch syndrome risk.

Jia X, Burugula BB, Chen V, Lemons RM, Jayakody S, Maksutova M, Kitzman JO.

Am J Hum Genet. 2021 Jan 7;108(1):163-175. doi: 10.1016/j.ajhg.2020.12.003. Epub 2020 Dec 23.

PubMed [citation]

PMID:: 33357406
PMCID:: PMC7820803

Details of each submission

From Ambry Genetics, SCV000275173.8

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

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 Sema4, Sema4, SCV002528814.1

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

#	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: Sep 29, 2024

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