ClinVar Miner

Submissions for variant NM_030578.4(B9D2):c.163_164delinsAA (p.Ala55Asn) (rs1555756363)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000533750 SCV000634627 uncertain significance Joubert syndrome; Meckel-Gruber syndrome 2017-04-11 criteria provided, single submitter clinical testing This sequence change deletes 2 nucleotides and inserts 2 nucleotides in exon 3 of the B9D2 mRNA (c.163_164delinsAA), replacing alanine with asparagine at codon 55 of the B9D2 protein (p.Ala55Asn). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and asparagine. This variant is reported as two separate single-nucleotide changes in the ExAC database (c.163G>A and c.164C>A), but the read data shows that the two variants are in cis, recapitulating the variant observed here (c.163_164delinsAA), in 2 individuals. It has not been reported in the literature in individuals with a B9D2-related disease Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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