ClinVar Miner

Submissions for variant NM_000297.4(PKD2):c.1445T>G (p.Phe482Cys)

gnomAD frequency: 0.00176  dbSNP: rs75762896
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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001080594 SCV000259367 benign Autosomal dominant polycystic kidney disease 2024-01-29 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV000244662 SCV000303527 likely benign not specified criteria provided, single submitter clinical testing
Eurofins Ntd Llc (ga) RCV000244662 SCV000331226 benign not specified 2015-08-03 criteria provided, single submitter clinical testing
Athena Diagnostics RCV000712679 SCV000843198 benign not provided 2018-06-05 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001001706 SCV001159282 benign Polycystic kidney disease 2 2020-05-07 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV001001706 SCV001429835 uncertain significance Polycystic kidney disease 2 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
GeneDx RCV000712679 SCV001782682 likely benign not provided 2021-01-15 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 32859249, 18257781, 27894351, 27884173, 18837007, 22995991, 22863349, 31349084)
CeGaT Center for Human Genetics Tuebingen RCV000712679 SCV004152956 benign not provided 2023-11-01 criteria provided, single submitter clinical testing PKD2: PM5, BP4, BS1, BS2
Department of Pathology and Laboratory Medicine, Sinai Health System RCV001292488 SCV001481081 likely benign Polycystic kidney disease no assertion criteria provided clinical testing The PKD2 p.Phe482Cys variant was identified in 7 of 954 proband chromosomes (frequency: 0.01) from individuals or families with ADPKD (Bataille 2011, Dedoussis 2008, Edrees 2016, Robinson 2012, Rossetti 2012, Tan 2008). The variant was also identified in the following databases: dbSNP (ID: rs75762896) as With other allele, ClinVar (classified as benign by Invitae; as likely benign by Prevention), Clinvitae , LOVD 3.0, ADPKD Mutation Database (classified as likely neutral). The variant was not identified in the COGR, or PKD1-LOVD databases. The variant was identified in control databases in 548 of 277128 chromosomes (3 homozygous) at a frequency of 0.002 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). Observations by population include African in 7 of 24034 chromosomes (freq: 0.0003), “Other” in 38 of 6462 chromosomes (freq: 0.01), Latino in 67 of 34416 chromosomes (freq: 0.002), EuropeanNon-Finnish in 302 of 126624 chromosomes (freq: 0.002), AshkenaziJewish in 102 of 10152 chromosomes (freq: 0.01), EuropeanFinnish in 3 of 25792 chromosomes (freq: 0.0001), and SouthAsian in 29 of 30782 chromosomes (freq: 0.001); it was not observed in the EastAsian population. The p.Phe482 residue is conserved in mammals but not in more distantly related organisms, and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) suggest that the variant may impact the protein; however, this information is not predictive enough to assume pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. The variant was identified with a co-occurring pathogenic PKD1 variant (IVS21–2delAG), increasing the likelihood that the p.Phe482Cys variant does not have clinical significance (Dedoussis 2008). In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000712679 SCV001741368 likely benign not provided no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000712679 SCV001931098 likely benign not provided no assertion criteria provided clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV000712679 SCV002035754 likely benign not provided no assertion criteria provided clinical testing

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