ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.4001+11_4001+15dup (rs587779302)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000160733 SCV000211369 benign Hereditary cancer-predisposing syndrome 2014-10-01 criteria provided, single submitter clinical testing The variant is found in BR-OV-HEREDIC,HEREDICANCER panel(s).
Invitae RCV000587529 SCV000253114 likely benign not provided 2015-05-15 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000074967 SCV000430981 uncertain significance Lynch syndrome 2016-06-14 criteria provided, single submitter clinical testing
Color Health, Inc RCV000160733 SCV000690426 likely benign Hereditary cancer-predisposing syndrome 2016-02-25 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000587529 SCV000695907 benign not provided 2016-12-01 criteria provided, single submitter clinical testing Variant summary: The MSH6 c.4001+11_4001+15dupAACTA variant results into duplication of five non-conserved nucleotides in intron 9 at a region not widely known to involve in splicing. Mutation taster predicts a benign outcome for this variant. In addition, 5/5 splice prediction tools predict no significant impact on normal splicing. This variant was found in 29/111750 control chromosomes from ExAC at a frequency of 0.0002595, which is approximately 2 times the estimated maximal expected allele frequency of a pathogenic MSH6 variant (0.0001421), suggesting this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories have classified this variant as likely benign/benign. The variant of interest has not, to our knowledge, been reported in affected individuals in literature. Taken together, this variant is classified as Benign.
Counsyl RCV000663009 SCV000786021 likely benign Hereditary nonpolyposis colorectal cancer type 5 2018-02-02 criteria provided, single submitter clinical testing
Mendelics RCV000074967 SCV000837930 uncertain significance Lynch syndrome 2018-07-02 criteria provided, single submitter clinical testing
Invitae RCV001463861 SCV001667811 likely benign Hereditary nonpolyposis colorectal neoplasms 2015-10-30 criteria provided, single submitter clinical testing
GeneDx RCV000587529 SCV001861252 benign not provided 2015-03-03 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000074967 SCV001550041 likely benign Lynch syndrome no assertion criteria provided clinical testing The MSH6 c.4001+11_4001+15dup variant was not identified in the literature nor was it identified in the UMD-LSDB database. The variant was identified in dbSNP (ID: rs730882138) as "With Likely benign, other allele" and ClinVar (classified as likely benign by Invitae, Counsyl and two other submitters). The variant was identified in control databases in 70 of 269486 chromosomes at a frequency of 0.0003, increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: South Asian in 23 of 30492 chromosomes (freq: 0.0008), European in 41 of 123358 chromosomes (freq: 0.0003), East Asian in 3 of 18612 chromosomes (freq: 0.0002), and Finnish in 3 of 23088 chromosomes (freq: 0.0001), while the variant was not observed in the African, Ashkenazi Jewish, Latino, or Other populations. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.

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