ClinVar Miner

Submissions for variant NM_001009944.3(PKD1):c.7275C>T (p.Gly2425=) (rs115772084)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PreventionGenetics,PreventionGenetics RCV000243205 SCV000305774 likely benign not specified criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000684768 SCV000810971 uncertain significance Polycystic kidney disease, adult type 2016-05-20 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000992599 SCV001145003 benign not provided 2018-09-30 criteria provided, single submitter clinical testing
GeneDx RCV000992599 SCV001889561 benign not provided 2020-04-30 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001292193 SCV001480917 likely benign Polycystic kidney disease no assertion criteria provided clinical testing The PKD1 p.Gly2425= variant was identified in 1 of 164 proband chromosomes (frequency: 0.006) from individuals or families with Autosomal Dominant PKD (Garcia-Gonzalez 2007). The variant was also identified in dbSNP (ID: rs115772084) as “With Likely benign allele”, ClinVar (as likely benign by Prevention Genetics which was then changed to uncertain significance in 2016), and ADPKD Mutation Database (as indeterminate). The variant was not identified in LOVD 3.0, or PKD1-LOVD. The variant was identified in control databases in 779 of 261798 chromosomes (6 homozygous) at a frequency of 0.002976 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 640 of 23178 chromosomes (freq: 0.02761), Other in 9 of 6270 chromosomes (freq: 0.001435), Latino in 57 of 34144 chromosomes (freq: 0.001669), European (Non-Finnish) in 18 of 122112 chromosomes (freq: 0.000147), Ashkenazi Jewish in 55 of 9964 chromosomes (freq: 0.00552), while the variant was not observed in the East Asian, European 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 p.Gly2425= 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 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) 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.

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