ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.1277-8T>C (rs145400590)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000201991 SCV000110270 benign not specified 2013-07-01 criteria provided, single submitter clinical testing
Invitae RCV000122980 SCV000166261 benign Hereditary nonpolyposis colorectal neoplasms 2020-12-06 criteria provided, single submitter clinical testing
GeneDx RCV000201991 SCV000170335 benign not specified 2013-11-05 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Ambry Genetics RCV000132507 SCV000187603 benign Hereditary cancer-predisposing syndrome 2019-05-30 criteria provided, single submitter clinical testing In silico models in agreement (benign);RNA Studies;Subpopulation frequency in support of benign classification
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000201991 SCV000601429 benign not specified 2017-04-24 criteria provided, single submitter clinical testing
Color Health, Inc RCV000132507 SCV000910604 benign Hereditary cancer-predisposing syndrome 2015-09-22 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001143791 SCV001304346 likely benign Lynch syndrome I 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001286995 SCV001473631 likely benign none provided 2019-10-11 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000201991 SCV000257135 uncertain significance not specified no assertion criteria provided research
True Health Diagnostics RCV000132507 SCV000788029 likely benign Hereditary cancer-predisposing syndrome 2017-10-10 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001358334 SCV001554038 likely benign Malignant tumor of breast no assertion criteria provided clinical testing The MSH2 c.1277-8T>C variant was not identified in the literature nor was it identified in the following databases: COGR, Cosmic, Zhejiang University Database, Mismatch Repair Genes Variant Database, or Insight Hereditary Tumors Database. The variant was identified in dbSNP (ID: rs145400590) as “With other allele”, in ClinVar (classified as benign by Invitae, GeneDx, and two clinical laboratories; as uncertain significance by Ambry Genetics, Mayo clinic), Clinvitae, and in UMD-LSDB (as neutral). The variant was identified in control databases in 154 of 275904 chromosomes (1 homozygous) at a frequency of 0.001 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). It was observed in the following populations: African in 114 of 23936 chromosomes (freq: 0.01), Other in 2 of 6434 chromosomes (freq: 0.0003), Latino in 20 of 34356 chromosomes (freq: 0.001), and European in 18 of 126058 chromosomes (freq: 0.0001); it was not observed in the Ashkenazi Jewish, East Asian, Finnish, and South Asian populations. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) 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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