NM_000179.3(MSH6):c.3717_3733del (p.Lys1240fs) AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 1, 2023
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:: RCV003594202.1

Allele description [Variation Report for NM_000179.3(MSH6):c.3717_3733del (p.Lys1240fs)]

NM_000179.3(MSH6):c.3717_3733del (p.Lys1240fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

2p16.3

Genomic location:

Preferred name:

NM_000179.3(MSH6):c.3717_3733del (p.Lys1240fs)

HGVS:

NC_000002.12:g.47806274_47806290del
NG_007111.1:g.28128_28144del
NG_008397.1:g.104389_104405del
NM_000179.3:c.3717_3733delMANE SELECT
NM_001281492.2:c.3327_3343del
NM_001281493.2:c.2811_2827del
NM_001281494.2:c.2811_2827del
NM_001406795.1:c.3813_3829del17
NM_001406796.1:c.3717_3733del17
NM_001406797.1:c.3420_3436del17
NM_001406798.1:c.3543_3559del17
NM_001406799.1:c.3192_3208del17
NM_001406800.1:c.3717_3733del17
NM_001406801.1:c.3420_3436del17
NM_001406802.1:c.3813_3829del17
NM_001406803.1:c.2853_2869del17
NM_001406804.1:c.3639_3655del17
NM_001406805.1:c.3420_3436del17
NM_001406806.1:c.3192_3208del17
NM_001406807.1:c.3192_3208del17
NM_001406808.1:c.3717_3733del17
NM_001406809.1:c.3717_3733del17
NM_001406811.1:c.2811_2827del17
NM_001406812.1:c.2811_2827del17
NM_001406813.1:c.3723_3739del17
NM_001406814.1:c.2811_2827del17
NM_001406815.1:c.2811_2827del17
NM_001406816.1:c.2811_2827del17
NM_001406817.1:c.2151_2167del17
NM_001406818.1:c.3420_3436del17
NM_001406819.1:c.3420_3436del17
NM_001406820.1:c.3420_3436del17
NM_001406821.1:c.3420_3436del17
NM_001406822.1:c.3420_3436del17
NM_001406823.1:c.2811_2827del17
NM_001406824.1:c.3420_3436del17
NM_001406825.1:c.3420_3436del17
NM_001406826.1:c.3549_3565del17
NM_001406827.1:c.3420_3436del17
NM_001406828.1:c.3420_3436del17
NM_001406829.1:c.2811_2827del17
NM_001406830.1:c.3420_3436del17
NM_001406831.1:c.498_514del17
NM_001406832.1:c.564_580del17
NM_001407362.1:c.1662_1678del17
NP_000170.1:p.Lys1240Phefs
NP_000170.1:p.Lys1240fs
NP_001268421.1:p.Lys1110fs
NP_001268422.1:p.Lys938fs
NP_001268423.1:p.Lys938fs
NP_001393724.1:p.Lys1272Phefs
NP_001393725.1:p.Lys1240Phefs
NP_001393726.1:p.Lys1141Phefs
NP_001393727.1:p.Lys1182Phefs
NP_001393728.1:p.Lys1065Phefs
NP_001393729.1:p.Lys1240Phefs
NP_001393730.1:p.Lys1141Phefs
NP_001393731.1:p.Lys1272Phefs
NP_001393732.1:p.Lys952Phefs
NP_001393733.1:p.Lys1214Phefs
NP_001393734.1:p.Lys1141Phefs
NP_001393735.1:p.Lys1065Phefs
NP_001393736.1:p.Lys1065Phefs
NP_001393737.1:p.Lys1240Phefs
NP_001393738.1:p.Lys1240Phefs
NP_001393740.1:p.Lys938Phefs
NP_001393741.1:p.Lys938Phefs
NP_001393742.1:p.Lys1242Phefs
NP_001393743.1:p.Lys938Phefs
NP_001393744.1:p.Lys938Phefs
NP_001393745.1:p.Lys938Phefs
NP_001393746.1:p.Lys718Phefs
NP_001393747.1:p.Lys1141Phefs
NP_001393748.1:p.Lys1141Phefs
NP_001393749.1:p.Lys1141Phefs
NP_001393750.1:p.Lys1141Phefs
NP_001393751.1:p.Lys1141Phefs
NP_001393752.1:p.Lys938Phefs
NP_001393753.1:p.Lys1141Phefs
NP_001393754.1:p.Lys1141Phefs
NP_001393755.1:p.Lys1184Phefs
NP_001393756.1:p.Lys1141Phefs
NP_001393757.1:p.Lys1141Phefs
NP_001393758.1:p.Lys938Phefs
NP_001393759.1:p.Lys1141Phefs
NP_001393760.1:p.Lys167Phefs
NP_001393761.1:p.Lys189Phefs
NP_001394291.1:p.Lys555Phefs
LRG_219t1:c.3717_3733del17
LRG_219:g.28128_28144del
LRG_219p1:p.Lys1240Phefs
NC_000002.11:g.48033410_48033426del
NC_000002.11:g.48033413_48033429del
NM_000179.2:c.3717_3733del17
NR_176256.1:n.2647_2663del17
NR_176257.1:n.3978_3994del17
NR_176258.1:n.3907_3923del17
NR_176259.1:n.3806_3822del17
NR_176260.1:n.1751_1767del17
NR_176261.1:n.3688_3704del17

Protein change:

K1110fs

Molecular consequence:

NM_000179.3:c.3717_3733del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001281492.2:c.3327_3343del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001281493.2:c.2811_2827del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001281494.2:c.2811_2827del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406795.1:c.3813_3829del17 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406796.1:c.3717_3733del17 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406797.1:c.3420_3436del17 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406798.1:c.3543_3559del17 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406799.1:c.3192_3208del17 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406800.1:c.3717_3733del17 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406801.1:c.3420_3436del17 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406802.1:c.3813_3829del17 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406803.1:c.2853_2869del17 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406804.1:c.3639_3655del17 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406805.1:c.3420_3436del17 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406806.1:c.3192_3208del17 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406807.1:c.3192_3208del17 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406808.1:c.3717_3733del17 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406809.1:c.3717_3733del17 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406811.1:c.2811_2827del17 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406812.1:c.2811_2827del17 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406813.1:c.3723_3739del17 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406814.1:c.2811_2827del17 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406815.1:c.2811_2827del17 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406816.1:c.2811_2827del17 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406817.1:c.2151_2167del17 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406818.1:c.3420_3436del17 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406819.1:c.3420_3436del17 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406820.1:c.3420_3436del17 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406821.1:c.3420_3436del17 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406822.1:c.3420_3436del17 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406823.1:c.2811_2827del17 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406824.1:c.3420_3436del17 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406825.1:c.3420_3436del17 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406826.1:c.3549_3565del17 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406827.1:c.3420_3436del17 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406828.1:c.3420_3436del17 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406829.1:c.2811_2827del17 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406830.1:c.3420_3436del17 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406831.1:c.498_514del17 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406832.1:c.564_580del17 - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001407362.1:c.1662_1678del17 - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Hereditary nonpolyposis colorectal neoplasms
Identifiers:: MeSH: D003123; MedGen: C0009405

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RFNG RFNG O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase [Homo sapiens]
RFNG RFNG O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase [Homo sapiens]
Gene ID:5986

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004253254	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 1, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 18269114, 24362816, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004253254

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 1, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

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

Germline MSH6 mutations are more prevalent in endometrial cancer patient cohorts than hereditary non polyposis colorectal cancer cohorts.

Devlin LA, Graham CA, Price JH, Morrison PJ.

Ulster Med J. 2008 Jan;77(1):25-30.

PubMed [citation]

PMID:: 18269114
PMCID:: PMC2397009

Application of a 5-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants in the InSiGHT locus-specific database.

Thompson BA, Spurdle AB, Plazzer JP, Greenblatt MS, Akagi K, Al-Mulla F, Bapat B, Bernstein I, Capellá G, den Dunnen JT, du Sart D, Fabre A, Farrell MP, Farrington SM, Frayling IM, Frebourg T, Goldgar DE, Heinen CD, Holinski-Feder E, Kohonen-Corish M, Robinson KL, Leung SY, et al.

Nat Genet. 2014 Feb;46(2):107-115. doi: 10.1038/ng.2854. Epub 2013 Dec 22.

PubMed [citation]

PMID:: 24362816
PMCID:: PMC4294709

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV004253254.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Lys1240Phefs*29) in the MSH6 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MSH6 are known to be pathogenic (PMID: 18269114, 24362816). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MSH6-related conditions. ClinVar contains an entry for this variant (Variation ID: 1734245). For these reasons, this variant has been classified as Pathogenic.

#	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: May 1, 2024

ClinVar

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