Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Athena Diagnostics Inc | RCV000992542 | SCV001144939 | benign | not provided | 2019-02-11 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV002496935 | SCV002810231 | benign | Polycystic kidney disease, adult type | 2021-08-23 | criteria provided, single submitter | clinical testing | |
| Department of Pathology and Laboratory Medicine, |
RCV000503255 | SCV000592841 | benign | Autosomal dominant polycystic kidney disease | no assertion criteria provided | clinical testing | The PKD1 p.Ser3373Ser variant was not identified in the literature nor was it identified in the in dbSNP, Clinvitae, ClinVar, GeneInsight COGR, MutDB, ADPKD Mutation Database, PKD1-LOVD, and PKD1-LOVD 3.0 databases. This variant was identified in the 1000 Genomes Project in 12 of 5000 chromosomes (frequency: 0.0024), HAPMAP populations: -SAS in 10 of 978 chromosomes (frequency: 0.0102)/ -AMR in 1 of 694 chromosomes (frequency: 0.0014)/ -AFR in 1 of 1322 chromosomes (frequency: 0.0008), NHLBI GO Exome Sequencing Project in 1 of 4362 African American alleles (frequency: 0.00022), and in the Exome Aggregation Consortium database (March 14, 2016) in 81 of 85286 chromosomes (freq. 00095) in the following populations: Other in 4 of 668 chromosomes (freq. 00599), South Asian in 53 (1 homozygous)of 14172 chromosomes (freq. 0.00374), African in 5 of 6322 chromosomes (freq. 0.00079), European (Non-Finnish) in 16 (1 homozygous) of 46062 chromosomes (freq. 0.00035), Latino in 2 of 7500 chromosomes (freq. 0.00027), East Asian in 1 of 6202 chromosomes (freq. 0.00016) but was not seen in European (Finnish) 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.” The p.Ser3373Ser 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. The variant was (also) identified by our laboratory in an individual with cystic kidney disease, co-occurring with a pathogenic PKD1 variant (c.6487C>T, p.Arg2163X), increasing the likelihood that the p.Ser3373Ser variant does not have clinical significance. In summary, based on the above information, this variant meets our laboratory's criteria to be classified as benign. |