ClinVar Miner

Submissions for variant NM_001195263.2(PDZD7):c.166dup (p.Arg56fs) (rs587776894)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001008540 SCV001168312 pathogenic not provided 2019-03-14 criteria provided, single submitter clinical testing The c.166dupC variant has been reported previously in trans with another PDZD7 variant in a family with hearing loss (Guan et al., 2018). It has also been reported as apparently de novo and heterozygous in a patient with Usher syndrome who was also homozygous for a variant in the USH2A gene; the authors proposed c.166dupC can serve as a phenoypic modifier in Usher syndrome (Ebermann et al., 2010). The duplication causes a frameshift starting with codon Arginine 56, changes this amino acid to a Proline residue and creates a premature Stop codon at position 24 of the new reading frame, denoted p.Arg56ProfsX24. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The variant is observed in 1/8716 (0.0115%) alleles from individuals of African background in large population cohorts (Lek et al., 2016). We interpret this variant as pathogenic.
Invitae RCV001008540 SCV001415224 pathogenic not provided 2019-10-13 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg56Profs*24) in the PDZD7 gene. It is expected to result in an absent or disrupted protein product. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been observed to segregate with autosomal recessive non-syndromic hearing loss in a family (PMID: 29048736). ClinVar contains an entry for this variant (Variation ID: 30983). Loss-of-function variants in PDZD7 are known to be pathogenic (PMID: 20440071). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000023974 SCV000045265 risk factor Usher syndrome, type 2A 2010-06-01 no assertion criteria provided literature only
OMIM RCV000656379 SCV000778390 pathogenic DEAFNESS, AUTOSOMAL RECESSIVE 57 2010-06-01 no assertion criteria provided literature only

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.