ClinVar Miner

Submissions for variant NM_024685.4(BBS10):c.646dup (p.Asp216fs) (rs1555202695)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000486438 SCV000567052 pathogenic not provided 2015-07-21 criteria provided, single submitter clinical testing The c.646dupG duplication in the BBS10 gene has not been reported previously as a pathogenic variant nor as a benign polymorphism, to our knowledge. The c.646dupG duplication causes a frameshiftstarting with codon Aspartic acid 216, changes this amino acid to a Glycine residue, and creates apremature Stop codon at position 39 of the new reading frame, denoted p.Asp216GlyfsX39. This variant is predicted to cause loss of normal protein function through protein truncation. The c.646dupG duplication was not observed in approximately 6,500 individuals of European and African American ancestry in theNHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Weinterpret c.646dupG as a pathogenic variant.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000826096 SCV000967599 likely pathogenic Bardet-Biedl syndrome 2018-12-26 criteria provided, single submitter clinical testing The p.Asp216GlyfsX39 variant in BBS10 has not been previously reported in indivi duals with Bardet-Biedl syndrome but has been reported in ClinVar (Variation ID: 419326). This variant was absent from large population studies. This variant is predicted to cause a frameshift, which alters the protein?s amino acid sequence beginning at position 216 and leads to a premature termination codon 39 amino a cids downstream. This alteration is then predicted to lead to a truncated or abs ent protein. Heterozygous loss of function of the BBS10 gene is an established d isease mechanism in Bardet-Biedl syndrome. In summary, although additional studi es are required to fully establish its clinical significance, the p.Asp216GlyfsX 39 variant is likely pathogenic. ACMG/AMP Criteria applied: PVS1, PM2.

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