NM_000179.3(MSH6):c.4002-10T>A AND Lynch syndrome 5

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Aug 22, 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:: RCV000986753.15

Allele description [Variation Report for NM_000179.3(MSH6):c.4002-10T>A]

NM_000179.3(MSH6):c.4002-10T>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.4002-10T>A

HGVS:

NC_000002.12:g.47806769T>A
NG_007111.1:g.28623T>A
NG_008397.1:g.103907A>T
NM_000179.3:c.4002-10T>AMANE SELECT
NM_001281492.2:c.3612-10T>A
NM_001281493.2:c.3096-10T>A
NM_001281494.2:c.3096-10T>A
LRG_219t1:c.4002-10T>A
LRG_219:g.28623T>A
NC_000002.11:g.48033908T>A
NM_000179.2:c.4002-10T>A

Links:

dbSNP: rs545466048

NCBI 1000 Genomes Browser:

rs545466048

Molecular consequence:

NM_000179.3:c.4002-10T>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001281492.2:c.3612-10T>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001281493.2:c.3096-10T>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001281494.2:c.3096-10T>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

Recent activity

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SH3-domain binding protein 5 (BTK-associated), isoform CRA_b [Rattus norvegicus]
SH3-domain binding protein 5 (BTK-associated), isoform CRA_b [Rattus norvegicus]
gi|149034181|gb|EDL88951.1||gnl|WGS |rCP21414

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001135868	Mendelics	criteria provided, single submitter (Mendelics Assertion Criteria 2019)	Benign (Aug 22, 2023)	germline	clinical testing	Citation Link,
SCV001300825	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Uncertain significance (Apr 18, 2019)	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

SCV001135868

Mendelics

criteria provided, single submitter

(Mendelics Assertion Criteria 2019)

Benign
(Aug 22, 2023)

germline

clinical testing

Citation Link,

SCV001300825

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Uncertain significance
(Apr 18, 2019)

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

Citations

PubMed

Prevalence of alterations in DNA mismatch repair genes in patients with young-onset colorectal cancer.

Limburg PJ, Harmsen WS, Chen HH, Gallinger S, Haile RW, Baron JA, Casey G, Woods MO, Thibodeau SN, Lindor NM.

Clin Gastroenterol Hepatol. 2011 Jun;9(6):497-502. doi: 10.1016/j.cgh.2010.10.021. Epub 2010 Nov 5.

PubMed [citation]

PMID:: 21056691
PMCID:: PMC3058119

Details of each submission

From Mendelics, SCV001135868.2

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

#	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 Illumina Laboratory Services, Illumina, SCV001300825.1

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

Description

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

#	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: Sep 16, 2024

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