NM_000251.3(MSH2):c.211+8C>T AND not specified

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Jan 12, 2018
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:: RCV000427874.5

Allele description [Variation Report for NM_000251.3(MSH2):c.211+8C>T]

NM_000251.3(MSH2):c.211+8C>T

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.211+8C>T

HGVS:

NC_000002.12:g.47403410C>T
NG_007110.2:g.5287C>T
NM_000251.3:c.211+8C>TMANE SELECT
NM_001258281.1:c.13+8C>T
LRG_218t1:c.211+8C>T
LRG_218:g.5287C>T
NC_000002.11:g.47630549C>T
NM_000251.1:c.211+8C>T
NM_000251.2:c.211+8C>T

Links:

dbSNP: rs267607916

NCBI 1000 Genomes Browser:

rs267607916

Molecular consequence:

NM_000251.3:c.211+8C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001258281.1:c.13+8C>T - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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wb [Aphidius gifuensis]
Gene ID:122855257

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000513648	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Benign (Aug 15, 2015)	germline	clinical testing	Citation Link,
SCV000917711	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Jan 12, 2018)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000513648

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Benign
(Aug 15, 2015)

germline

clinical testing

Citation Link,

SCV000917711

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Jan 12, 2018)

germline

clinical testing

Citation Link

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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	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From GeneDx, SCV000513648.4

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

Description

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

#	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

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000917711.1

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

Description

Variant summary: The MSH2 c.211+8C>T variant involves the alteration of a non-conserved intronic nucleotide and 4/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts the elimination of ESE binding sites. However, these predictions have yet to be confirmed by functional studies. This variant was found in 10/242066 control chromosomes (gnomAD), predominantly observed in the European (Non-Finnish) subpopulation at a frequency of 0.000092 (10/108416). This frequency does not exceed the estimated maximal expected allele frequency of a pathogenic MSH2 variant (0.0005683). Multiple clinical diagnostic laboratories classified this variant as "likely benign/benign." The variant of interest has not, to our knowledge, been reported in affected individuals via publications. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a "Variant of Uncertain Significance - Possibly Benign," until additional information becomes available.

#	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 8, 2024

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