NM_000251.3(MSH2):c.(211+1_212-1)_(1076+1_1077-1)del (p.Gly71Aspfs*2) AND Lynch syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Sep 5, 2013
Review status:: 3 stars out of maximum of 4 stars
reviewed by expert panel

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:: RCV000076397.4

Allele description [Variation Report for NM_000251.3(MSH2):c.(211+1_212-1)_(1076+1_1077-1)del (p.Gly71Aspfs*2)]

NM_000251.3(MSH2):c.(211+1_212-1)_(1076+1_1077-1)del (p.Gly71Aspfs*2)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

2p21

Genomic location:

Chr2: 47630542 - 47656880 (on Assembly GRCh37)

Preferred name:

NM_000251.3(MSH2):c.(211+1_212-1)_(1076+1_1077-1)del (p.Gly71Aspfs*2)

HGVS:

LRG_218t1:c.212-?_1076+?del
NC_000002.11:g.(47630542_47635539)_(47643569_47656880)del
NM_000251.1:c.212-?_1076+?del
NM_000251.2:c.212-?_1076+?del

Links:

LOVD 3: MSH2_000088

Condition(s)

Name:: Lynch syndrome
Identifiers:: MONDO: MONDO:0005835; MedGen: C4552100

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000107422	International Society for Gastrointestinal Hereditary Tumours (InSiGHT)	reviewed by expert panel (Guidelines v1.9)	Pathogenic (Sep 5, 2013)	germline	research	Citation Link,
SCV000253803	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 4, 2015)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000107422

International Society for Gastrointestinal Hereditary Tumours (InSiGHT)

reviewed by expert panel

(Guidelines v1.9)

Pathogenic
(Sep 5, 2013)

germline

research

Citation Link,

SCV000253803

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 4, 2015)

germline

clinical testing

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

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, research

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From International Society for Gastrointestinal Hereditary Tumours (InSiGHT), SCV000107422.3

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

Description

Large deletion

#	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 Invitae, SCV000253803.2

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

Description

This sequence change is a gross deletion of the genomic region encompassing exons 2-6 of the MSH2 gene. This deletion extends to both edges of the assayed region, and the exact 5' and 3' boundaries of this event are not known but are most likely contained somewhere within intron 1 and intron 6. Loss of function variants in MSH2 are known to be pathogenic. A deletion of exons 2-6 has been observed in an individual with colorectal cancer and two affected members of a Lynch Syndrome family (PMID: 15949572, 8808596). For these reasons, this variant has been classified as Pathogenic.

#	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: Mar 26, 2023

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