ClinVar Miner

Submissions for variant NM_001009944.3(PKD1):c.5648C>T (p.Ala1883Val) (rs779745348)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000757644 SCV000885944 uncertain significance not provided 2017-12-11 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000757644 SCV001144992 likely benign not provided 2018-12-13 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001292266 SCV001480925 likely benign Polycystic kidney disease no assertion criteria provided clinical testing The PKD1 p.Ala1883Val variant was not identified in the literature nor was it identified in the dbSNP, LOVD 3.0, ADPKD Mutation Database, PKD1-LOVD, databases. The variant was identified in ClinVar (classified as uncertain significance by ARUP). The variant was identified in control databases in 48 of 270388 chromosomes at a frequency of 0.0002 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017), observed in the following populations: African in 4 of 23300 chromosomes (freq: 0.0002), Latino in 1 of 34152 chromosomes (freq: 0.00003), European Non-Finnish in 40 of 122664 chromosomes (freq: 0.0003), East Asian in 2 of 18700 chromosomes (freq: 0.0001), European Finnish in 1 of 24824 chromosomes (freq: 0.00004), while not observed in the Other, Ashkenazi Jewish, 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.Ala1883 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood the variant Val impacts 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 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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