ClinVar Miner

Submissions for variant NM_001009944.3(PKD1):c.6545A>G (p.Gln2182Arg)

gnomAD frequency: 0.00492  dbSNP: rs147685291
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000503788 SCV000614518 benign not specified 2017-02-20 criteria provided, single submitter clinical testing
Mendelics RCV000989455 SCV001139785 likely benign Polycystic kidney disease, adult type 2019-05-28 criteria provided, single submitter clinical testing
GeneDx RCV001675911 SCV001894521 benign not provided 2020-04-01 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 17574468, 22995991)
Department of Pathology and Laboratory Medicine, Sinai Health System RCV001291840 SCV000592793 likely benign Polycystic kidney disease no assertion criteria provided clinical testing The PKD1 p.Gln2182Arg variant was identified in 2 of 164 proband chromosomes (frequency: 0.012) from individuals or families with polycystic kidney disease, and was not identified in 342 control chromosomes from healthy individuals. The variant was also identified in dbSNP (ID: rs147685291) as “NA”, in Cosmic 1x as a variant of unknown origin from a lung cell carcinoma and in ADPKD database as likely neutral. The variant was also identified in the 1000 Genomes Project in 31 of 5000 chromosomes (frequency: 0.0062); the NHLBI GO Exome Sequencing Project in 1 of 8452 European American (frequency: 0.0001) and 57 of 4274 African American alleles (frequency: 0.01). Furthermore the variant was identified in the Exome Aggregation Consortium database (August 8, 2016) in 83 (2 homozygous) of 24342 chromosomes (frequency: 0.003) in the following populations: African in 80 of 2954 chromosomes (frequency: 0.027), Latino in 3 of 798 chromosomes (frequency: 0.004), but was not seen in East Asian, European (Finnish), European (Non-Finnish) and South Asian populations. In addition we cannot be certain that data from control databases is specific to PKD1 and not from one of the six PKD1 pseudogenes. The variant was not identified in Clinvitae, ClinVar, GeneInsight COGR, MutDB, PKD1-LOVD and PKD1-LOVD 3.0 databases. The p.Gln2182 residue is conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of 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. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant as Likely Benign.

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