U.S. flag

An official website of the United States government

NM_000179.3(MSH6):c.3556+5_3556+8delinsCATTATTGTCAGG AND Lynch syndrome 1

Germline classification:
Uncertain significance (1 submission)
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV001726531.2

Allele description [Variation Report for NM_000179.3(MSH6):c.3556+5_3556+8delinsCATTATTGTCAGG]

NM_000179.3(MSH6):c.3556+5_3556+8delinsCATTATTGTCAGG

Gene:
MSH6:mutS homolog 6 [Gene - OMIM - HGNC]
Variant type:
Indel
Cytogenetic location:
2p16.3
Genomic location:
Preferred name:
NM_000179.3(MSH6):c.3556+5_3556+8delinsCATTATTGTCAGG
HGVS:
  • NC_000002.12:g.47805032_47805035delinsCATTATTGTCAGG
  • NG_007111.1:g.26886_26889delinsCATTATTGTCAGG
  • NG_008397.1:g.105641_105644delinsCCTGACAATAATG
  • NM_000179.3:c.3556+5_3556+8delinsCATTATTGTCAGGMANE SELECT
  • NM_001281492.2:c.3166+5_3166+8delinsCATTATTGTCAGG
  • NM_001281493.2:c.2650+5_2650+8delinsCATTATTGTCAGG
  • NM_001281494.2:c.2650+5_2650+8delinsCATTATTGTCAGG
  • LRG_219t1:c.3556+5_3556+8delinsCATTATTGTCAGG
  • LRG_219:g.26886_26889delinsCATTATTGTCAGG
  • NC_000002.11:g.48032171_48032174delinsCATTATTGTCAGG
  • NM_000179.2:c.3556+5_3556+8delGTTTinsCATTATTGTCAGG
  • NM_000179.2:c.3556+5_3556+8delinsCATTATTGTCAGG
Links:
dbSNP: rs2104510542
NCBI 1000 Genomes Browser:
rs2104510542
Molecular consequence:
  • NM_000179.3:c.3556+5_3556+8delinsCATTATTGTCAGG - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001281492.2:c.3166+5_3166+8delinsCATTATTGTCAGG - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001281493.2:c.2650+5_2650+8delinsCATTATTGTCAGG - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001281494.2:c.2650+5_2650+8delinsCATTATTGTCAGG - intron variant - [Sequence Ontology: SO:0001627]
Observations:
1

Condition(s)

Name:
Lynch syndrome 1
Synonyms:
COLON CANCER, FAMILIAL NONPOLYPOSIS, TYPE 1; MSH2-Related Hereditary Non-Polyposis Colon Cancer; Lynch syndrome I; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0007356; MedGen: C2936783; Orphanet: 144; OMIM: 120435

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001571514Kids Neuroscience Centre, Sydney Children's Hospitals Network
criteria provided, single submitter

(Bournazos AM et al. (Genet Med 2021))		Uncertain significanceunknownclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownyes1not providednot provided1not providedclinical testing

Citations

PubMed

Standardized practices for RNA diagnostics using clinically accessible specimens reclassifies 75% of putative splicing variants.

Bournazos AM, Riley LG, Bommireddipalli S, Ades L, Akesson LS, Al-Shinnag M, Alexander SI, Archibald AD, Balasubramaniam S, Berman Y, Beshay V, Boggs K, Bojadzieva J, Brown NJ, Bryen SJ, Buckley MF, Chong B, Davis MR, Dawes R, Delatycki M, Donaldson L, Downie L, et al.

Genet Med. 2022 Jan;24(1):130-145. doi: 10.1016/j.gim.2021.09.001. Epub 2021 Nov 30.

PubMed [citation]
PMID:
34906502

Details of each submission

From Kids Neuroscience Centre, Sydney Children's Hospitals Network, SCV001571514.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)

Description

Out-of-frame exon 6 skipping (r.3439_3556del) causes a frameshift encoding 8 missense amino acids and a premature termination codon (p.(Ala1147Valfs*9)). These transcripts are predicted to be targeted by nonsens e mediated decay (NMD). Any mis-spliced transcipts that escape NMD encode MSH6 protein lacking 215 amino acids from the C -terminus, including 180 amino acids from the MutS domain. Intron 6 retention (r.3556_3557ins[3556+1_3557-1]) causes a frameshift encoding 16 missense amino acids and a premature termination codon (p.(Glu1187Aspfs*17)). These transcripts are predicted to be targeted by NMD. Any mis spliced transcipts that escape NMD encode MSH6 protein lacking 174 amino acids from the C -terminus, including 139 amino acids from the MutS domain.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownyes1Whole bloodnot provided1not providednot providednot provided

Last Updated: Jun 9, 2024