NM_000179.3(MSH6):c.3646+1G>A AND Lynch syndrome 5

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Aug 24, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV002243498.3

Allele description [Variation Report for NM_000179.3(MSH6):c.3646+1G>A]

NM_000179.3(MSH6):c.3646+1G>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.3646+1G>A

HGVS:

NC_000002.12:g.47805708G>A
NG_007111.1:g.27562G>A
NG_008397.1:g.104968C>T
NM_000179.3:c.3646+1G>AMANE SELECT
NM_001281492.2:c.3256+1G>A
NM_001281493.2:c.2740+1G>A
NM_001281494.2:c.2740+1G>A
NM_001406795.1:c.3742+1G>A
NM_001406796.1:c.3646+1G>A
NM_001406797.1:c.3349+1G>A
NM_001406798.1:c.3472+1G>A
NM_001406799.1:c.3121+1G>A
NM_001406800.1:c.3646+1G>A
NM_001406801.1:c.3349+1G>A
NM_001406802.1:c.3742+1G>A
NM_001406803.1:c.2782+1G>A
NM_001406804.1:c.3568+1G>A
NM_001406805.1:c.3349+1G>A
NM_001406806.1:c.3121+1G>A
NM_001406807.1:c.3121+1G>A
NM_001406808.1:c.3646+1G>A
NM_001406809.1:c.3646+1G>A
NM_001406811.1:c.2740+1G>A
NM_001406812.1:c.2740+1G>A
NM_001406813.1:c.3652+1G>A
NM_001406814.1:c.2740+1G>A
NM_001406815.1:c.2740+1G>A
NM_001406816.1:c.2740+1G>A
NM_001406817.1:c.2080+1G>A
NM_001406818.1:c.3349+1G>A
NM_001406819.1:c.3349+1G>A
NM_001406820.1:c.3349+1G>A
NM_001406821.1:c.3349+1G>A
NM_001406822.1:c.3349+1G>A
NM_001406823.1:c.2740+1G>A
NM_001406824.1:c.3349+1G>A
NM_001406825.1:c.3349+1G>A
NM_001406826.1:c.3478+1G>A
NM_001406827.1:c.3349+1G>A
NM_001406828.1:c.3349+1G>A
NM_001406829.1:c.2740+1G>A
NM_001406830.1:c.3349+1G>A
NM_001406831.1:c.427+1G>A
NM_001406832.1:c.493+1G>A
NM_001407362.1:c.1591+1G>A
LRG_219:g.27562G>A
NC_000002.11:g.48032847G>A

Links:

dbSNP: rs1553332772

NCBI 1000 Genomes Browser:

rs1553332772

Molecular consequence:

NM_000179.3:c.3646+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001281492.2:c.3256+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001281493.2:c.2740+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001281494.2:c.2740+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406795.1:c.3742+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406796.1:c.3646+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406797.1:c.3349+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406798.1:c.3472+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406799.1:c.3121+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406800.1:c.3646+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406801.1:c.3349+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406802.1:c.3742+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406803.1:c.2782+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406804.1:c.3568+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406805.1:c.3349+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406806.1:c.3121+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406807.1:c.3121+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406808.1:c.3646+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406809.1:c.3646+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406811.1:c.2740+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406812.1:c.2740+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406813.1:c.3652+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406814.1:c.2740+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406815.1:c.2740+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406816.1:c.2740+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406817.1:c.2080+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406818.1:c.3349+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406819.1:c.3349+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406820.1:c.3349+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406821.1:c.3349+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406822.1:c.3349+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406823.1:c.2740+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406824.1:c.3349+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406825.1:c.3349+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406826.1:c.3478+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406827.1:c.3349+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406828.1:c.3349+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406829.1:c.2740+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406830.1:c.3349+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406831.1:c.427+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406832.1:c.493+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407362.1:c.1591+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

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
SCV002512138	Human Genetics Unit, University Of Colombo	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jun 20, 2020)	germline	research	PubMed (1) [See all records that cite this PMID]
SCV004189272	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Likely pathogenic (Aug 24, 2023)	unknown	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002512138

Human Genetics Unit, University Of Colombo

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jun 20, 2020)

germline

research

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

SCV004189272

Myriad Genetics, Inc.

criteria provided, single submitter

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

Likely pathogenic
(Aug 24, 2023)

unknown

clinical testing

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Human Genetics Unit, University Of Colombo, SCV002512138.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	Sinhalese	not provided	not provided	not provided	research	PubMed (1)

Description

This null variant (canonical +1 splice site) was discovered in a 53 year old colorectal cancer affected female. It was not found in the local exome database at HGU nor in global population frequency databases. This variant is classified as Pathogenic (Ic) with the evidences: PVS1, PM2, PP3 according to ACMG-AMP criteria.

#	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 Myriad Genetics, Inc., SCV004189272.1

#	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 pathogenic. This variant occurs within a consensus splice junction and is predicted to result in abnormal mRNA splicing of either an out-of-frame exon or an in-frame exon necessary for protein stability and/or normal function.

#	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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