ClinVar Miner

Submissions for variant NM_001009944.3(PKD1):c.8020C>T (p.Pro2674Ser) (rs144557371)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PreventionGenetics,PreventionGenetics RCV000251247 SCV000305784 likely benign not specified criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000999801 SCV000604778 benign Polycystic kidney disease, adult type 2020-04-04 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000755610 SCV001145013 benign not provided 2019-03-18 criteria provided, single submitter clinical testing
GeneDx RCV000755610 SCV001911337 benign not provided 2019-12-30 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 22008521, 17574468, 11115377, 32457805)
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001291879 SCV000592810 benign Polycystic kidney disease no assertion criteria provided clinical testing The PKD1 p.Pro2674Ser variant was identified in 11 of 586 proband chromosomes (frequency: 0.02) from individuals with Autosomal Dominant Polycystic Kidney Disease (Bataille 2011, Garcia-Gonzalez 2007, Rossetti 2001). The variant was identified in dbSNP (rs144557371) as “with other allele”, ClinVar (interpreted as likely benign by our laboratory and 1 other submitter; and as benign by ARUP Laboratories), LOVD 3.0 (observed 2x) and ADPKD Mutation Database (observed 1x). The variant was not identified in PKD1-LOVD. The variant was identified in control databases in 1570 of 151,230 chromosomes (10 homozygous) at a frequency of 0.01, increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 26 of 13,758 chromosomes (freq: 0.002), Other in 52 of 4316 chromosomes (freq: 0.01), Latino in 155 of 24,266 chromosomes (freq: 0.006), European in 986 of 60,346 chromosomes (freq: 0.01), Ashkenazi Jewish in 58 of 7264 chromosomes (freq: 0.008), Finnish in 273 of 9002 chromosomes (freq: 0.03), and South Asian in 20 of 20,846 chromosomes (freq: 0.001); it was not observed in the East Asian population. 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 p.Pro2674 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information, this variant meets our laboratory criteria to be classified as benign.
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000251247 SCV001931058 benign not specified no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000251247 SCV001959789 benign not specified no assertion criteria provided clinical testing

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