ClinVar Miner

Submissions for variant NM_025077.4(TOE1):c.-45G>A (rs2275602)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000126892 SCV000170423 benign not specified 2014-02-28 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.
PreventionGenetics,PreventionGenetics RCV000126892 SCV000306737 benign not specified criteria provided, single submitter clinical testing
Color Health, Inc RCV000579941 SCV000685614 benign Hereditary cancer-predisposing syndrome 2016-05-03 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000126892 SCV001159238 benign not specified 2019-03-27 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001097390 SCV001253668 uncertain significance MYH-associated polyposis 2018-02-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Invitae RCV001097390 SCV001728679 benign MYH-associated polyposis 2020-12-06 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001353844 SCV000592671 likely benign Carcinoma of colon no assertion criteria provided clinical testing The MUTYH c.36+11C>T variant was identified in 7 of 276 proband chromosomes (frequency: 0.04) from individuals or families with (Shinmura 2014,Tao 2004, Zhou 2005). The variant was also identified in dbSNP (ID: rs2275602) as "With other allele", in ClinVar (3x as Benign by GeneDx, Colour Genomics and Prevention Genetics), Insight Colon Cancer Gene Variant Database (4x), and in UMD-LSDB (2x as unclassified variant). The variant was also identified by our laboratory in 7 individuals including 6 with a clinical indication for hereditary colon cancer testing. The variant was not identified in GeneInsight-COGR, Cosmic, or MutDB databases. The variant was identified in control databases in 914 of 275438 chromosomes (11 homozygous) at a frequency of 0.003 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: African in 2 of 23810 chromosomes (freq: 0.00008), Other in 17 of 6424 chromosomes (freq: 0.003), Latino in 3 of 34366 chromosomes (freq: 0.00009), European Non-Finnish in 133 of 125622 chromosomes (freq: 0.001), East Asian in 467 of 18808 chromosomes (freq: 0.02), Finnish in 213 of 25526 chromosomes (freq: 0.008), and South Asian in 79 of 30766 chromosomes (freq: 0.003), while the variant was not observed in the Ashkenazi Jewish population. 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; however, the c.36+11C>T variant is located in the boundary region between MUTYH exon 1 and intron 1 and many reports have suggested that gene variants in the neighborhood of the junction are often accompanied by abnormal splicing (Tao 2008). In a Japanese population-based study, a statistically significant association was demonstrated between this variant and increased CRC risk (Tao 2008). Moreover, one haplotype containing the variant c.36+11T was demonstrated to be associated with increased CRC risk (OR of 1.43, haplotype .36+11C>T, c.504+35A>G, c.934−2A>G, and c.1014G>C, “TGAC”). The c.36+11C>T variant was found to be in complete linkage disequilibrium with two other MUTYH variants, –280G>A and c.1389G>C. These results indicate that individuals with the MUTYH – 280A/c.36+11T/c.1431C genotypes or the TGAC haplotype are susceptible to CRC (Tao 2008). 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.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV001573000 SCV001798247 likely benign not provided no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV000126892 SCV001809044 benign not specified no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000126892 SCV001955783 benign not specified no assertion criteria provided clinical testing

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