Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Prevention |
RCV000245362 | SCV000305763 | likely benign | not specified | criteria provided, single submitter | clinical testing | ||
| Fulgent Genetics, |
RCV002500873 | SCV002798350 | likely benign | Polycystic kidney disease, adult type | 2021-08-02 | criteria provided, single submitter | clinical testing | |
| Department of Pathology and Laboratory Medicine, |
RCV001292430 | SCV001480900 | likely benign | Polycystic kidney disease | no assertion criteria provided | clinical testing | The PKD1 p.Arg2121Arg variant was identified in 1 of 164 proband chromosomes (frequency: 0.006) from individuals or families with ADPKD (Garcia-Gonzalez 2007). The variant was also identified in dbSNP (ID: rs138648495) as “With Likely benign allele”, ClinVar (1x, as likely benign by Prevention Genetics), ADPKD Mutation Database (as likely neutral). The variant was not identified in the LOVD 3.0 or PKD1-LOVD databases. The variant was identified in control databases in 205 of 199160 (2 homozygous) chromosomes at a frequency of 0.001029 in the following populations: African greater than 1%, in 189 of 17490 chromosomes (freq. 0.0108), other in 4 of 5062 chromosomes (freq. 0.0008), Latino in 7 of 27584 chromosomes (freq. 0.00025), increasing the likelihood that this may be a low frequency benign variant in certain populations of origin (Genome Aggregation Consortium Feb 27, 2017). 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 also identified in our laboratory in one individual with ADPKD, co-occurring pathogenic PKD1 variant (c.8017-?_8161+?del), increasing the likelihood that the p.Arg2121Arg variant does not have clinical significance. The p.Arg2121Arg 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 addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) 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. |