ClinVar Miner

Submissions for variant NM_001195263.2(PDZD7):c.2107del (p.Ser703fs)

dbSNP: rs397516633
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000037097 SCV000060754 likely pathogenic Rare genetic deafness 2019-02-11 criteria provided, single submitter clinical testing proposed classification - variant undergoing re-assessment, contact laboratory
GeneDx RCV000599609 SCV000710015 pathogenic not provided 2022-09-13 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 20440071, 29048736, 26849169, 31454969)
Invitae RCV000599609 SCV001211134 pathogenic not provided 2024-01-19 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser703Valfs*20) in the PDZD7 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PDZD7 are known to be pathogenic (PMID: 20440071). This variant is present in population databases (rs397516633, gnomAD 0.06%). This premature translational stop signal has been observed in individual(s) with non-syndromic hearing loss (PMID: 26849169). ClinVar contains an entry for this variant (Variation ID: 44121). For these reasons, this variant has been classified as Pathogenic.
UNC Molecular Genetics Laboratory, University of North Carolina at Chapel Hill RCV000656355 SCV001423849 likely pathogenic Hearing loss, autosomal recessive 57 criteria provided, single submitter research The PDZD7 c.2107delA [p.S703fs] frameshift variant is predicted to result in premature truncation and/or absence of the PDZD7 protein and has previously been reported in prelingual, non-syndromic autosomal recessive hearing loss (PMID: 26849169).
DASA RCV001849292 SCV002107080 pathogenic Usher syndrome, type IIC, GPR98/PDZD7 digenic 2022-03-05 criteria provided, single submitter clinical testing The c.2107delA;p.(Ser703Valfs*20) is a null frameshift variant (NMD) in the PDZD7 gene and predicts alteration of the nonsense-mediate decay - NMD is present in a relevant exon to the transcript - PVS1. This sequence change has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 44121; PMID: 26849169; PMID: 20440071) - PS4. The variant is present at low allele frequencies population databases (rs397516633 – gnomAD 0.003017%; ABraOM 0.001281 frequency - http://abraom.ib.usp.br/) - PM2_supporting. The p.(Ser703Valfs*20) was detected in trans with a pathogenic variant (PMID: 26849169) and was detected in a homozygous state in the analyzed sample - PM3. The variant co-segregated with disease in multiple affected family members (PMID: 26849169) - PP1. In summary, the currently available evidence indicates that the variant is pathogenic.
Fulgent Genetics, Fulgent Genetics RCV002490502 SCV002797720 likely pathogenic Usher syndrome type 2C; Usher syndrome type 2A; Hearing loss, autosomal recessive 57 2022-03-28 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003398601 SCV004106050 pathogenic PDZD7-related condition 2023-01-03 criteria provided, single submitter clinical testing The PDZD7 c.2107delA variant is predicted to result in a frameshift and premature protein termination (p.Ser703Valfs*20). This variant has been reported as pathogenic in patients with non-syndromic hearing loss (Vona et al. 2016. PubMed ID: 26849169; Cruz Marino et al. 2021. PubMed ID: 34387732). This variant is reported in 0.060% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/10-102770538-CT-C). Frameshift variants in PDZD7 are expected to be pathogenic and this variant has been interpreted as pathogenic or likely pathogenic by multiple independent submitters to the ClinVar database (https://www.ncbi.nlm.nih.gov/clinvar/variation/44121). We interpret this variant as pathogenic.
OMIM RCV000656355 SCV000778328 pathogenic Hearing loss, autosomal recessive 57 2018-06-04 no assertion criteria provided literature only

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