NM_000251.3(MSH2):c.108_159del (p.Phe37fs) AND Hereditary cancer-predisposing syndrome

This record was updated by the submitter. Please see the current version.

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Feb 19, 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:: RCV002417562.1

Allele description

NM_000251.3(MSH2):c.108_159del (p.Phe37fs)

Gene:

MSH2:mutS homolog 2 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

2p21

Genomic location:

Preferred name:

NM_000251.3(MSH2):c.108_159del (p.Phe37fs)

HGVS:

NC_000002.12:g.47403299_47403350del
NG_007110.2:g.5176_5227del
NG_095167.1:g.503_554del
NM_000251.3:c.108_159delMANE SELECT
NM_001258281.1:c.-30-61_-30-10del
NM_001406631.1:c.108_159del52
NM_001406632.1:c.108_159del52
NM_001406633.1:c.108_159del52
NM_001406634.1:c.108_159del52
NM_001406635.1:c.108_159del52
NM_001406636.1:c.108_159del52
NM_001406637.1:c.108_159del52
NM_001406638.1:c.108_159del52
NM_001406639.1:c.108_159del52
NM_001406640.1:c.108_159del52
NM_001406641.1:c.108_159del52
NM_001406642.1:c.108_159del52
NM_001406643.1:c.108_159del52
NM_001406644.1:c.108_159del52
NM_001406645.1:c.108_159del52
NM_001406646.1:c.108_159del52
NM_001406647.1:c.108_159del52
NM_001406648.1:c.108_159del52
NM_001406649.1:c.108_159del52
NM_001406650.1:c.108_159del52
NM_001406651.1:c.108_159del52
NM_001406652.1:c.108_159del52
NM_001406653.1:c.108_159del52
NM_001406654.1:c.-233_-182del52
NM_001406655.1:c.108_159del52
NM_001406656.1:c.-888_-837del52
NM_001406657.1:c.108_159del52
NM_001406658.1:c.-1211_-1160del52
NM_001406659.1:c.-1361_-1310del52
NM_001406660.1:c.-1558_-1507del52
NM_001406661.1:c.-1513_-1462del52
NM_001406662.1:c.-1430_-1379del52
NM_001406666.1:c.108_159del52
NM_001406669.1:c.-1361_-1310del52
NM_001406672.1:c.108_159del52
NM_001406674.1:c.108_159del52
NP_000242.1:p.Phe37Profs
NP_000242.1:p.Phe37fs
NP_001393560.1:p.Phe37Profs
NP_001393561.1:p.Phe37Profs
NP_001393562.1:p.Phe37Profs
NP_001393563.1:p.Phe37Profs
NP_001393564.1:p.Phe37Profs
NP_001393565.1:p.Phe37Profs
NP_001393566.1:p.Phe37Profs
NP_001393567.1:p.Phe37Profs
NP_001393568.1:p.Phe37Profs
NP_001393569.1:p.Phe37Profs
NP_001393570.1:p.Phe37Profs
NP_001393571.1:p.Phe37Profs
NP_001393572.1:p.Phe37Profs
NP_001393573.1:p.Phe37Profs
NP_001393574.1:p.Phe37Profs
NP_001393575.1:p.Phe37Profs
NP_001393576.1:p.Phe37Profs
NP_001393577.1:p.Phe37Profs
NP_001393578.1:p.Phe37Profs
NP_001393579.1:p.Phe37Profs
NP_001393580.1:p.Phe37Profs
NP_001393581.1:p.Phe37Profs
NP_001393582.1:p.Phe37Profs
NP_001393584.1:p.Phe37Profs
NP_001393586.1:p.Phe37Profs
NP_001393595.1:p.Phe37Profs
NP_001393601.1:p.Phe37Profs
NP_001393603.1:p.Phe37Profs
LRG_218t1:c.108_159del52
LRG_218:g.5176_5227del
LRG_218p1:p.Phe37Profs
NC_000002.11:g.47630438_47630489del
NM_000251.1:c.108_159del52
NM_000251.2:c.108_159del52
NR_176230.1:n.144_195del52
NR_176231.1:n.144_195del52
NR_176232.1:n.144_195del52
NR_176233.1:n.144_195del52
NR_176234.1:n.144_195del52
NR_176235.1:n.144_195del52
NR_176236.1:n.144_195del52
NR_176237.1:n.144_195del52
NR_176238.1:n.144_195del52
NR_176239.1:n.144_195del52
NR_176240.1:n.144_195del52
NR_176241.1:n.144_195del52
NR_176242.1:n.144_195del52
NR_176243.1:n.144_195del52
NR_176244.1:n.144_195del52
NR_176245.1:n.144_195del52
NR_176246.1:n.144_195del52
NR_176247.1:n.144_195del52
NR_176248.1:n.144_195del52
NR_176249.1:n.144_195del52
NR_176250.1:n.144_195del52

Protein change:

F37fs

Molecular consequence:

NM_000251.3:c.108_159del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406631.1:c.108_159del52 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406632.1:c.108_159del52 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406633.1:c.108_159del52 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406634.1:c.108_159del52 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406635.1:c.108_159del52 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406636.1:c.108_159del52 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406637.1:c.108_159del52 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406638.1:c.108_159del52 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406639.1:c.108_159del52 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406640.1:c.108_159del52 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406641.1:c.108_159del52 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406642.1:c.108_159del52 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406643.1:c.108_159del52 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406644.1:c.108_159del52 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406645.1:c.108_159del52 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406646.1:c.108_159del52 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406647.1:c.108_159del52 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406648.1:c.108_159del52 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406649.1:c.108_159del52 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406650.1:c.108_159del52 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406651.1:c.108_159del52 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406652.1:c.108_159del52 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406653.1:c.108_159del52 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406655.1:c.108_159del52 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406657.1:c.108_159del52 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406666.1:c.108_159del52 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406672.1:c.108_159del52 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406674.1:c.108_159del52 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001258281.1:c.-30-61_-30-10del - intron variant - [Sequence Ontology: SO:0001627]

Observations:

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
SCV002726416	Ambry Genetics	criteria provided, single submitter (Ambry General Variant Classification Scheme_2022)	Likely pathogenic (Feb 19, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002726416

Ambry Genetics

criteria provided, single submitter

(Ambry General Variant Classification Scheme_2022)

Likely pathogenic
(Feb 19, 2021)

germline

clinical testing

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

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	1	not provided	not provided	1	not provided	clinical testing

Citations

PubMed

Mechanism of mismatch recognition revealed by human MutSβ bound to unpaired DNA loops.

Gupta S, Gellert M, Yang W.

Nat Struct Mol Biol. 2011 Dec 18;19(1):72-8. doi: 10.1038/nsmb.2175.

PubMed [citation]

PMID:: 22179786
PMCID:: PMC3252464

Details of each submission

From Ambry Genetics, SCV002726416.1

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

Description

The c.108_159del52 variant, located in coding exon 1 of the MSH2 gene, results from a deletion of 52 nucleotides at nucleotide positions 108 to 159, causing a translational frameshift with a predicted alternate stop codon (p.F37Pfs*10). The predicted stop codon occurs within the first 150 nucleotides of the MSH2 gene. This alteration may escape nonsense-mediated mRNA decay and/or be rescued by re-initiation (Rivas et al. Science. 2015 May 8;348(6235):666-9; Lindeboom et al. Nat Genet. 2016 Oct;48(10):1112-8; Rhee et al. Sci Rep. 2017 May 10;7(1):1653). However, the impacted region is critical for protein function and a significant portion of the protein is affected. (Ambry internal data). Based on internal structural analysis, this variant is anticipated to result in a disruption in ligand and protein binding (Ambry internal data; Gupta S et al. Nat Struct Mol Biol, 2011 Dec;19:72-8). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. Based on the majority of available evidence to date, this variant is likely to be pathogenic.

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

Last Updated: Dec 24, 2023

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