ClinVar Miner

Submissions for variant NM_000283.4(PDE6B):c.1927_1948del (p.Asn643fs)

gnomAD frequency: 0.00010  dbSNP: rs1325957874
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV002246264 SCV002518774 pathogenic Congenital stationary night blindness autosomal dominant 2 2022-05-04 criteria provided, single submitter clinical testing
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard RCV001267698 SCV001445948 likely pathogenic Retinitis pigmentosa 40 2020-11-16 no assertion criteria provided curation The heterozygous p.Asn643GlyfsTer7 variant in PDE6B was identified by our study in the compound heterozygous state, along with a variant of unknown significance, in 1 individual with retinitis pigmentosa. The variant has not been previously reported in individuals with retinitis pigmentosa but has been identified in 0.0007841% (1/127532) of European non-Finnish chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs1296042817). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 643 and leads to a premature termination codon 7 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function of the PDE6B gene is an established disease mechanism in autosomal recessive retinitis pigmentosa 40. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic. ACMG/AMP Criteria applied: PVS1, PM2 (Richards 2015).

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