Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_025114.4(CEP290):āc.2268A>Gā(p.Ser756=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.9 in 1,558,632 control chromosomes in the GnomAD database, including 641,375 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ). Synonymous variant affecting the same amino acid position (i.e. S756S) has been classified as Likely benign.
CEP290 (HGNC:29021): (centrosomal protein 290) This gene encodes a protein with 13 putative coiled-coil domains, a region with homology to SMC chromosome segregation ATPases, six KID motifs, three tropomyosin homology domains and an ATP/GTP binding site motif A. The protein is localized to the centrosome and cilia and has sites for N-glycosylation, tyrosine sulfation, phosphorylation, N-myristoylation, and amidation. Mutations in this gene have been associated with Joubert syndrome and nephronophthisis and the presence of antibodies against this protein is associated with several forms of cancer. [provided by RefSeq, Jul 2008]
Computational evidence support a benign effect (BayesDel_noAF=-0.59).
BP6
Variant 12-88111301-T-C is Benign according to our data. Variant chr12-88111301-T-C is described in ClinVar as [Benign]. Clinvar id is 126249.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-88111301-T-C is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=0.347 with no splicing effect.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.943 is higher than 0.05.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
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Benign, no assertion criteria provided
clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
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Likely benign, no assertion criteria provided
clinical testing
Genetic Services Laboratory, University of Chicago
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Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Senior-Loken syndrome 6 Benign:1
Benign, criteria provided, single submitter
clinical testing
Genome-Nilou Lab
Jul 22, 2021
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Leber congenital amaurosis Benign:1
Benign, no assertion criteria provided
clinical testing
Natera, Inc.
Sep 16, 2020
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Bardet-Biedl syndrome 14 Benign:1
Benign, criteria provided, single submitter
clinical testing
Genome-Nilou Lab
Jul 22, 2021
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Meckel-Gruber syndrome;C0431399:Familial aplasia of the vermis;C0687120:Nephronophthisis Benign:1