ClinVar Miner

Submissions for variant NM_025114.4(CEP290):c.1079G>A (p.Arg360Gln)

gnomAD frequency: 0.00405  dbSNP: rs188164241
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Total submissions: 20
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins NTD LLC (GA) RCV000152980 SCV000202421 likely benign not specified 2015-02-10 criteria provided, single submitter clinical testing
Invitae RCV001084283 SCV000253610 likely benign Joubert syndrome; Meckel-Gruber syndrome; Nephronophthisis 2021-12-18 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000152980 SCV000314512 likely benign not specified criteria provided, single submitter clinical testing
GeneDx RCV000152980 SCV000512568 likely benign not specified 2017-11-06 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.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000658663 SCV000602964 likely benign not provided 2017-05-05 criteria provided, single submitter clinical testing The CEP290 c.1079G>A;p.Arg360Gln variant has not been listed in the medical literature or in gene-specific databases. The variant is listed in the ClinVar database (Variation ID: 166838) and the dbSNP variant database (rs188164241) with an allele frequency of 0.3471 percent (39/11197 alleles) in the Exome Variant Server and 0.5192 percent (575/110744 alleles) in the Genome Aggregation Database. The amino acid at this position is moderately conserved across species but computational algorithms do not reach a consensus as to the effect of this variant (SIFT: Tolerated, PolyPhen2: Probably Damaging, Align GVGD: C0). Considering all available information, this variant is classified as likely benign.
CeGaT Center for Human Genetics Tuebingen RCV000658663 SCV000780446 likely benign not provided 2022-01-01 criteria provided, single submitter clinical testing
Mendelics RCV000988890 SCV001138788 likely benign Joubert syndrome 1 2019-05-28 criteria provided, single submitter clinical testing
Illumina Laboratory Services,Illumina RCV001110567 SCV001268017 uncertain significance Bardet-Biedl syndrome 14 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services,Illumina RCV001110568 SCV001268018 uncertain significance Meckel syndrome, type 4 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services,Illumina RCV001110569 SCV001268019 likely benign Senior-Loken syndrome 6 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.
Illumina Laboratory Services,Illumina RCV001110570 SCV001268020 uncertain significance Joubert syndrome 5 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services,Illumina RCV001110571 SCV001268021 uncertain significance Leber congenital amaurosis 10 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Genome-Nilou Lab RCV001110567 SCV001781516 uncertain significance Bardet-Biedl syndrome 14 2021-07-14 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001110570 SCV001781517 uncertain significance Joubert syndrome 5 2021-07-14 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001110568 SCV001781518 uncertain significance Meckel syndrome, type 4 2021-07-14 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001110569 SCV001781519 uncertain significance Senior-Loken syndrome 6 2021-07-14 criteria provided, single submitter clinical testing
Genetic Services Laboratory,University of Chicago RCV000152980 SCV002068810 likely benign not specified 2019-08-16 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000152980 SCV002500310 uncertain significance not specified 2022-03-10 criteria provided, single submitter clinical testing Variant summary: CEP290 c.1079G>A (p.Arg360Gln) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0039 in 150552 control chromosomes in the gnomAD database, including 4 homozygotes (gnomAD v3.1.2). c.1079G>A has been reported in the literature in two homozygous individuals affected with type 2 diabetes (Lim_2014) and in heterozygous individuals affected with Leber congenital amaurosis and left ventricular outflow defects (Haer-Wigman_2017, Watkins_2019). In addition, the variant has been reported in a cerebellar ataxia case along with another CEP290 pathogenic variant (Coutelier_2018) and in an individual affected with a rare disorder (exact phenotype not specified) in compound heterozygosity with a pathogenic variant (Stranneheim_2021). These reports do not provide unequivocal conclusions about association of the variant with CEP290-Related Disorders. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Nine ClinVar submitters (evaluation after 2014) cite the variant as likely benign and two ClinVar submitters (evaluation after 2014) cite it as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance until additional evidence of clinical and/or functional importance become available.
Genome Diagnostics Laboratory,The Hospital for Sick Children RCV002294046 SCV002587716 uncertain significance Atypical hemolytic-uremic syndrome 2017-08-17 criteria provided, single submitter clinical testing
Natera, Inc. RCV001275040 SCV001459794 likely benign Leber congenital amaurosis 2020-04-17 no assertion criteria provided clinical testing

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