NM_000179.3(MSH6):c.3801+5G>A AND Lynch syndrome 5

Germline classification:: Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:: Mar 28, 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:: RCV000411771.8

Allele description [Variation Report for NM_000179.3(MSH6):c.3801+5G>A]

NM_000179.3(MSH6):c.3801+5G>A

Gene:

MSH6:mutS homolog 6 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2p16.3

Genomic location:

Preferred name:

NM_000179.3(MSH6):c.3801+5G>A

HGVS:

NC_000002.12:g.47806363G>A
NG_007111.1:g.28217G>A
NG_008397.1:g.104313C>T
NM_000179.3:c.3801+5G>AMANE SELECT
NM_001281492.2:c.3411+5G>A
NM_001281493.2:c.2895+5G>A
NM_001281494.2:c.2895+5G>A
LRG_219t1:c.3801+5G>A
LRG_219:g.28217G>A
NC_000002.11:g.48033502G>A
NM_000179.2:c.3801+5G>A

Links:

dbSNP: rs201080919

NCBI 1000 Genomes Browser:

rs201080919

Molecular consequence:

NM_000179.3:c.3801+5G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001281492.2:c.3411+5G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001281493.2:c.2895+5G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001281494.2:c.2895+5G>A - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: Lynch syndrome 5 (LYNCH5)
Synonyms:: Colorectal cancer, hereditary nonpolyposis, type 5; Hereditary non-polyposis colorectal cancer, type 5
Identifiers:: MONDO: MONDO:0013710; MedGen: C1833477; Orphanet: 144; OMIM: 614350

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000430980	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Uncertain significance (Jan 13, 2018)	germline	clinical testing	Citation Link,
SCV000488861	Counsyl	criteria provided, single submitter (Counsyl Autosomal Dominant Disease Classification criteria (2015))	Uncertain significance (Sep 7, 2016)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 26976419, 25318351 Counsyl Autosomal Dominant Disease Classification criteria (2015), Citation Link,
SCV004018878	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Likely benign (Mar 28, 2023)	unknown	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

SCV000430980

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Uncertain significance
(Jan 13, 2018)

germline

clinical testing

Citation Link,

SCV000488861

Counsyl

criteria provided, single submitter

(Counsyl Autosomal Dominant Disease Classification criteria (2015))

Uncertain significance
(Sep 7, 2016)

unknown

clinical testing

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

Counsyl Autosomal Dominant Disease Classification criteria (2015),

Citation Link,

SCV004018878

Myriad Genetics, Inc.

criteria provided, single submitter

(Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))

Likely benign
(Mar 28, 2023)

unknown

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

Citations

PubMed

Frequency of Germline Mutations in 25 Cancer Susceptibility Genes in a Sequential Series of Patients With Breast Cancer.

Tung N, Lin NU, Kidd J, Allen BA, Singh N, Wenstrup RJ, Hartman AR, Winer EP, Garber JE.

J Clin Oncol. 2016 May 1;34(13):1460-8. doi: 10.1200/JCO.2015.65.0747. Epub 2016 Mar 14.

PubMed [citation]

PMID:: 26976419
PMCID:: PMC4872307

Use of panel tests in place of single gene tests in the cancer genetics clinic.

Yorczyk A, Robinson LS, Ross TS.

Clin Genet. 2015 Sep;88(3):278-82. doi: 10.1111/cge.12488. Epub 2014 Oct 16.

PubMed [citation]

PMID:: 25318351

See all PubMed Citations (3)

Details of each submission

From Illumina Laboratory Services, Illumina, SCV000430980.3

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

Description

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.

#	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 Counsyl, SCV000488861.2

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

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

From Myriad Genetics, Inc., SCV004018878.1

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

Description

This variant is considered likely benign. This variant is strongly associated with less severe personal and family histories of cancer, typical for individuals without pathogenic variants in this gene [PMID: 25085752].

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

Last Updated: Oct 8, 2024

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