Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV001095103 | SCV000451566 | likely benign | Polycystic kidney disease 2 | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. |
| Invitae | RCV000367425 | SCV001010986 | benign | Autosomal dominant polycystic kidney disease | 2023-11-20 | criteria provided, single submitter | clinical testing | |
| Prevention |
RCV003922538 | SCV004745717 | benign | PKD2-related condition | 2019-06-07 | criteria provided, single submitter | clinical testing | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). |
| Department of Pathology and Laboratory Medicine, |
RCV001292304 | SCV001480583 | likely benign | Polycystic kidney disease | no assertion criteria provided | clinical testing | The PKD2 p.Gln938= variant was not identified in the literature nor was it identified in the COGR, LOVD 3.0 or PKD1-LOVD databases. The variant was identified in dbSNP (ID: rs573469832) as “With Uncertain significance allele”, ClinVar (classified as uncertain significance by Illumina), and ADPKD Mutation Database (classified as likely neutral). The variant was identified in control databases in 332 of 277086 chromosomes (1 homozygous) at a frequency of 0.001 increasing the likelihood this could be a low frequency benign variant in certain populations of origin (Genome Aggregation Database Feb 27, 2017). It was observed in the following populations: South Asian in 319 of 30780 chromosomes (freq: 0.01), African in 1 of 24034 chromosomes (freq: 0.00004), Other in 2 of 6464 chromosomes (freq: 0.0003), Latino in 6 of 34414 chromosomes (freq: 0.0002), and European Non-Finnish in 4 of 126596 chromosomes (freq: 0.00003); it was not observed in the Ashkenazi Jewish, East Asian, or European Finnish populations. The p.Gln938= variant has been observed by our laboratory in one individual with a co-occurring pathogenic PKD2 variant (p.Leu288IlefsX15). The p.Gln938= 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. 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. |