NM_000251.3(MSH2):c.277C>T (p.Leu93Phe) AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 8, 2021
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV002465507.1

Allele description [Variation Report for NM_000251.3(MSH2):c.277C>T (p.Leu93Phe)]

NM_000251.3(MSH2):c.277C>T (p.Leu93Phe)

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.277C>T (p.Leu93Phe)

HGVS:

NC_000002.12:g.47408466C>T
NG_007110.2:g.10343C>T
NM_000251.3:c.277C>TMANE SELECT
NM_001258281.1:c.79C>T
NP_000242.1:p.Leu93Phe
NP_000242.1:p.Leu93Phe
NP_001245210.1:p.Leu27Phe
LRG_218t1:c.277C>T
LRG_218:g.10343C>T
LRG_218p1:p.Leu93Phe
NC_000002.11:g.47635605C>T
NM_000251.1:c.277C>T
NM_000251.2:c.277C>T
P43246:p.Leu93Phe

Protein change:

L27F

Links:

UniProtKB: P43246#VAR_043743; dbSNP: rs63751429

NCBI 1000 Genomes Browser:

rs63751429

Molecular consequence:

NM_000251.3:c.277C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001258281.1:c.79C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary nonpolyposis colorectal neoplasms
Identifiers:: MeSH: D003123; MedGen: C0009405

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002760189	Cancer Variant Interpretation Group UK, Institute of Cancer Research, London	criteria provided, single submitter (Garrett et al. (J Med Genet. 2021))	Uncertain significance (Oct 8, 2021)	germline	curation	PubMed (2) [See all records that cite these PMIDs] 33208383, 1589646

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002760189

Cancer Variant Interpretation Group UK, Institute of Cancer Research, London

criteria provided, single submitter

(Garrett et al. (J Med Genet. 2021))

Uncertain significance
(Oct 8, 2021)

germline

curation

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	curation

Citations

PubMed

Combining evidence for and against pathogenicity for variants in cancer susceptibility genes: CanVIG-UK consensus recommendations.

Garrett A, Durkie M, Callaway A, Burghel GJ, Robinson R, Drummond J, Torr B, Cubuk C, Berry IR, Wallace AJ, Ellard S, Eccles DM, Tischkowitz M, Hanson H, Turnbull C; CanVIG-UK..

J Med Genet. 2021 May;58(5):297-304. doi: 10.1136/jmedgenet-2020-107248. Epub 2020 Nov 18.

PubMed [citation]

PMID:: 33208383
PMCID:: PMC8086256

[Evaluation of myocardial oxygen extraction dynamics in syndrome X by continuous measurement of coronary sinus oxygen saturation and its relation to clinical features].

Mikuniya A, Fujino Y, Higashiyama A, Narita T, Fukushi T, Sasaki M, Onodera K, Sawai M, Akitsu H, Oike Y.

Kokyu To Junkan. 1992 May;40(5):473-80. Japanese.

PubMed [citation]

PMID:: 1589646

Details of each submission

From Cancer Variant Interpretation Group UK, Institute of Cancer Research, London, SCV002760189.1

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

Description

Data included in classification: Absent from 118479 gnomAD v.2.1.1 non-cancer WES samples (PM2_mod) Revel: 0.87 (PP3_sup) Baudi et al., 2005, PMID: 15896463 – 2 case family with colorectal cancer at 27 & 43, both tumours MSI high and with loss of MSH2 on IHC (PP4_mod) Jia et al., 2021, PMID: 33357406 – functional (BS3_str) Data not included in classification: Drost et al., 2019, PMID: 30504929 – uncertain (original assay)/benign (multiple repeats) Classification as likely pathogenic by expert group (InSiGHT, 3* review, June 2019) as mostly based on Baudi et al., 2005 cases Bonadona et al., 201,1 PMID: 21642682 – Lynch syndrome family – no variant level phenotype information 7 Observations in LOVD Not seen in 2841 UK diagnostic tests

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Dec 24, 2023

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