ClinVar Miner

Submissions for variant NM_001009944.3(PKD1):c.2289_2299del (p.Cys767fs)

dbSNP: rs2092600667
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Molecular Genetics of Inherited Kidney Disorders Laboratory, Garvan Institute of Medical Research RCV001249128 SCV001422401 likely pathogenic not provided 2019-01-01 criteria provided, single submitter clinical testing
Molecular Genetics, Royal Melbourne Hospital RCV003994244 SCV004812842 pathogenic Autosomal dominant polycystic kidney disease 2024-03-01 criteria provided, single submitter clinical testing This sequence change in PKD1 is a frameshift variant predicted to cause a premature stop codon, p.(Cys767Alafs*27), in biologically relevant exon 11/46 leading to nonsense-mediated decay in a gene in which loss-of-function is an established disease mechanism. This variant is absent from the population database gnomAD v4.0. This variant has been reported in at least two unrelated individuals with a clinical diagnosis of autosomal dominant polycystic kidney disease (PMID: 21115670, 33437033). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.6.1, this variant is classified as PATHOGENIC. Following criteria are met: PVS1, PM2_Supporting, PS4_Moderate
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute RCV004789494 SCV005398937 pathogenic Polycystic kidney disease, adult type 2024-10-08 criteria provided, single submitter clinical testing Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with polycystic kidney disease 1 (MIM#173900). (I) 0107 - This gene is associated with autosomal dominant disease. Polycystic kidney disease 1 (MIM#173900) is predominantly caused by monoallelic variants, with rare reports of biallelic variants causing disease (OMIM). (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0701 - Other NMD-predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity. There are many NMD-predicted variants in PKD1 with strong evidence for pathogenicity (DECIPHER). (SP) 0802 - This variant has moderate previous evidence of pathogenicity in unrelated individuals. This variant has been classified as likely pathogenic in ClinVar, and has been observed in multiple unrelated individuals in the literature with polycystic kidney disease (PMID: 21115670, 22508176). (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign
Fulgent Genetics, Fulgent Genetics RCV004789494 SCV005643130 pathogenic Polycystic kidney disease, adult type 2024-01-08 criteria provided, single submitter clinical testing

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