ClinVar Miner

Submissions for variant NM_030578.4(B9D2):c.463G>A (p.Gly155Ser)

dbSNP: rs750436680
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
UW Hindbrain Malformation Research Program, University of Washington RCV000201776 SCV000256285 pathogenic Familial aplasia of the vermis 2015-02-23 criteria provided, single submitter research
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001844085 SCV002104006 likely pathogenic Joubert syndrome and related disorders 2022-02-18 criteria provided, single submitter clinical testing Variant summary: B9D2 c.463G>A (p.Gly155Ser) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 250880 control chromosomes (gnomAD). The variant, c.463G>A, has been reported in the literature in a compound heterozygous individual affected with Joubert Syndrome, who carried the variant c.220C>T (p.Pro74Ser) in trans (Bachmann-Gagescu_2015). A recent publication reported experimental evidence characterizing both variants alone and together in a C. elegans model system, and demonstrated that the cellular level, localization and function were moderately (P74S) or severely (G155S) altered, confirming that both variant alleles are pathogenic in worms, and compound heterozygous worms phenocopy worms homozygous for P74S (Lange_2021). One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
OMIM RCV002265681 SCV000611603 pathogenic Joubert syndrome 34 2015-08-01 no assertion criteria provided literature only

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