U.S. flag

An official website of the United States government

NM_000179.3(MSH6):c.2534_2538del (p.Met844_Tyr845insTer) AND Lynch syndrome

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
May 8, 2019
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:
RCV004017990.1

Allele description [Variation Report for NM_000179.3(MSH6):c.2534_2538del (p.Met844_Tyr845insTer)]

NM_000179.3(MSH6):c.2534_2538del (p.Met844_Tyr845insTer)

Gene:
MSH6:mutS homolog 6 [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
2p16.3
Genomic location:
Preferred name:
NM_000179.3(MSH6):c.2534_2538del (p.Met844_Tyr845insTer)
HGVS:
  • NC_000002.12:g.47800517_47800521del
  • NG_007111.1:g.22371_22375del
  • NM_000179.3:c.2534_2538delMANE SELECT
  • NM_001281492.2:c.2144_2148del
  • NM_001281493.2:c.1628_1632del
  • NM_001281494.2:c.1628_1632del
  • NM_001406795.1:c.2630_2634del
  • NM_001406796.1:c.2534_2538del
  • NM_001406797.1:c.2237_2241del
  • NM_001406798.1:c.2534_2538del
  • NM_001406799.1:c.2009_2013del
  • NM_001406800.1:c.2534_2538del
  • NM_001406801.1:c.2237_2241del
  • NM_001406802.1:c.2630_2634del
  • NM_001406803.1:c.2308+226_2308+230del
  • NM_001406804.1:c.2456_2460del
  • NM_001406805.1:c.2237_2241del
  • NM_001406806.1:c.2009_2013del
  • NM_001406807.1:c.2009_2013del
  • NM_001406808.1:c.2534_2538del
  • NM_001406809.1:c.2534_2538del
  • NM_001406811.1:c.1628_1632del
  • NM_001406812.1:c.1628_1632del
  • NM_001406813.1:c.2540_2544del
  • NM_001406814.1:c.1628_1632del
  • NM_001406815.1:c.1628_1632del
  • NM_001406816.1:c.1628_1632del
  • NM_001406817.1:c.1606+928_1606+932del
  • NM_001406818.1:c.2237_2241del
  • NM_001406819.1:c.2237_2241del
  • NM_001406820.1:c.2237_2241del
  • NM_001406821.1:c.2237_2241del
  • NM_001406822.1:c.2237_2241del
  • NM_001406823.1:c.1628_1632del
  • NM_001406824.1:c.2237_2241del
  • NM_001406825.1:c.2237_2241del
  • NM_001406826.1:c.2366_2370del
  • NM_001406827.1:c.2237_2241del
  • NM_001406828.1:c.2237_2241del
  • NM_001406829.1:c.1628_1632del
  • NM_001406830.1:c.2237_2241del
  • NM_001407362.1:c.628-149_628-145del
  • NP_000170.1:p.Met844_Tyr845insTer
  • NP_000170.1:p.Tyr845Terfs
  • NP_001268421.1:p.Met714_Tyr715insTer
  • NP_001268422.1:p.Met542_Tyr543insTer
  • NP_001268423.1:p.Met542_Tyr543insTer
  • NP_001393724.1:p.Met876_Tyr877insTer
  • NP_001393725.1:p.Met844_Tyr845insTer
  • NP_001393726.1:p.Met745_Tyr746insTer
  • NP_001393727.1:p.Met844_Tyr845insTer
  • NP_001393728.1:p.Met669_Tyr670insTer
  • NP_001393729.1:p.Met844_Tyr845insTer
  • NP_001393730.1:p.Met745_Tyr746insTer
  • NP_001393731.1:p.Met876_Tyr877insTer
  • NP_001393733.1:p.Met818_Tyr819insTer
  • NP_001393734.1:p.Met745_Tyr746insTer
  • NP_001393735.1:p.Met669_Tyr670insTer
  • NP_001393736.1:p.Met669_Tyr670insTer
  • NP_001393737.1:p.Met844_Tyr845insTer
  • NP_001393738.1:p.Met844_Tyr845insTer
  • NP_001393740.1:p.Met542_Tyr543insTer
  • NP_001393741.1:p.Met542_Tyr543insTer
  • NP_001393742.1:p.Met846_Tyr847insTer
  • NP_001393743.1:p.Met542_Tyr543insTer
  • NP_001393744.1:p.Met542_Tyr543insTer
  • NP_001393745.1:p.Met542_Tyr543insTer
  • NP_001393747.1:p.Met745_Tyr746insTer
  • NP_001393748.1:p.Met745_Tyr746insTer
  • NP_001393749.1:p.Met745_Tyr746insTer
  • NP_001393750.1:p.Met745_Tyr746insTer
  • NP_001393751.1:p.Met745_Tyr746insTer
  • NP_001393752.1:p.Met542_Tyr543insTer
  • NP_001393753.1:p.Met745_Tyr746insTer
  • NP_001393754.1:p.Met745_Tyr746insTer
  • NP_001393755.1:p.Met788_Tyr789insTer
  • NP_001393756.1:p.Met745_Tyr746insTer
  • NP_001393757.1:p.Met745_Tyr746insTer
  • NP_001393758.1:p.Met542_Tyr543insTer
  • NP_001393759.1:p.Met745_Tyr746insTer
  • LRG_219t1:c.2534_2538del
  • LRG_219:g.22371_22375del
  • LRG_219p1:p.Tyr845Terfs
  • NC_000002.11:g.48027656_48027660del
  • NC_000002.12:g.47800517_47800521delATGAA
  • NM_000179.2:c.2534_2538delATGAA
  • NR_176256.1:n.1396_1400del
  • NR_176257.1:n.2623_2627del
  • NR_176258.1:n.2623_2627del
  • NR_176259.1:n.2623_2627del
  • NR_176261.1:n.2623_2627del
Molecular consequence:
  • NM_001406803.1:c.2308+226_2308+230del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001406817.1:c.1606+928_1606+932del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001407362.1:c.628-149_628-145del - intron variant - [Sequence Ontology: SO:0001627]
  • NR_176256.1:n.1396_1400del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_176257.1:n.2623_2627del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_176258.1:n.2623_2627del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_176259.1:n.2623_2627del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_176261.1:n.2623_2627del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NM_000179.3:c.2534_2538del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001281492.2:c.2144_2148del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001281493.2:c.1628_1632del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001281494.2:c.1628_1632del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001406795.1:c.2630_2634del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001406796.1:c.2534_2538del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001406797.1:c.2237_2241del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001406798.1:c.2534_2538del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001406799.1:c.2009_2013del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001406800.1:c.2534_2538del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001406801.1:c.2237_2241del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001406802.1:c.2630_2634del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001406804.1:c.2456_2460del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001406805.1:c.2237_2241del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001406806.1:c.2009_2013del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001406807.1:c.2009_2013del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001406808.1:c.2534_2538del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001406809.1:c.2534_2538del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001406811.1:c.1628_1632del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001406812.1:c.1628_1632del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001406813.1:c.2540_2544del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001406814.1:c.1628_1632del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001406815.1:c.1628_1632del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001406816.1:c.1628_1632del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001406818.1:c.2237_2241del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001406819.1:c.2237_2241del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001406820.1:c.2237_2241del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001406821.1:c.2237_2241del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001406822.1:c.2237_2241del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001406823.1:c.1628_1632del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001406824.1:c.2237_2241del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001406825.1:c.2237_2241del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001406826.1:c.2366_2370del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001406827.1:c.2237_2241del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001406828.1:c.2237_2241del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001406829.1:c.1628_1632del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001406830.1:c.2237_2241del - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Lynch syndrome
Identifiers:
MONDO: MONDO:0005835; MedGen: C4552100

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
SCV004847758Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely Pathogenic
(May 8, 2019) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

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 Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV004847758.1

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

Description

The p.Tyr845X variant in MSH6 has not been previously reported in individuals with Lynch Syndrome and was absent from large population studies. This nonsense variant leads to a premature termination codon at position 845, which is predicted to lead to a truncated or absent protein. Heterozygous loss of function of the MSH6 gene is an established disease mechanism in individuals with Lynch syndrome. In summary, this variant meets criteria to be classified as likely pathogenic for autosomal dominant Lynch syndrome. ACMG/AMP criteria applied: PVS1, PM2.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 8, 2024