ClinVar Miner

Submissions for variant NM_001009944.3(PKD1):c.8364G>A (p.Ser2788=)

gnomAD frequency: 0.00128  dbSNP: rs145176597
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PreventionGenetics, part of Exact Sciences RCV000251699 SCV000305793 likely benign not specified criteria provided, single submitter clinical testing
Athena Diagnostics RCV000251699 SCV000614546 benign not specified 2017-03-13 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000757637 SCV000885937 benign Polycystic kidney disease, adult type 2019-03-08 criteria provided, single submitter clinical testing
Ambry Genetics RCV003258716 SCV003955286 likely benign Inborn genetic diseases 2023-05-19 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
CeGaT Center for Human Genetics Tuebingen RCV001727657 SCV004142836 likely benign not provided 2024-11-01 criteria provided, single submitter clinical testing PKD1: BP4, BP7
Breakthrough Genomics, Breakthrough Genomics RCV001727657 SCV005217047 likely benign not provided criteria provided, single submitter not provided
Department of Pathology and Laboratory Medicine, Sinai Health System RCV001292040 SCV001480656 likely benign Polycystic kidney disease no assertion criteria provided clinical testing The PKD1 p.Ser2788= variant was identified in 1 of 460 proband chromosomes (freq 0.002) from individuals or families with PKD (Rossetti 2012). The variant was also identified in dbSNP (ID: rs145176597) as “With Likely benign allele”, in Clinvitae and ClinVar (as likely benign by PreventionGenetics), ADPKD Mutation Database (as likely neutral), and PKD1-LOVD 3.0 (2x, unclassified with the probability of no functional affect), the 1000 Genomes Project in 4 of 5008 chromosomes (freq 0.0008), the NHLBI GO Exome Sequencing Project in 20 of 8446 European American alleles (freq 0.0023) and 2 in 4306 African American alleles (freq 0.00045), the genome Aggregation Database (beta, October 19th 2016) in 286 (1 homozygous) of 271612 chromosomes (freq. 0.001), the Exome Aggregation Consortium database (August 8th 2016) in 108 (1 homozygous) of 113342 chromosomes (freq. 0.001) in the following populations: European in 84 of 61652 chromosomes (freq. 0.001), South Asian in 13 of 16422 chromosomes (freq. 0.0008), Latino in 8 of 11282 chromosomes (freq. 0.0007), African in 2 of 8270 chromosomes (freq. 0.00024), and East Asian in 1 of 8378 chromosomes (freq. 0.0001), but was not seen in Finnish and other populations, increasing the likelihood this could be a low frequency benign variant. In addition we cannot be certain that data from control databases is specific to PKD1 and not from one of the six PKD1 pseudogenes. This variant was not identified in GeneInsight-COGR, MutDB, and PKD1-LOVD databases. The p.Ser2788= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. The variant occurs outside of the splicing consensus sequence and 1 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. 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.
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000251699 SCV001927558 benign not specified no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV001727657 SCV001973896 likely benign not provided no assertion criteria provided clinical testing

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