Total submissions: 9
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Athena Diagnostics Inc | RCV000516393 | SCV000614520 | benign | not specified | 2020-10-28 | criteria provided, single submitter | clinical testing | |
| ARUP Laboratories, |
RCV001287782 | SCV001474511 | likely benign | Polycystic kidney disease, adult type | 2019-09-06 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV001287782 | SCV002802858 | likely benign | Polycystic kidney disease, adult type | 2021-11-01 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002525060 | SCV003574854 | uncertain significance | Inborn genetic diseases | 2021-06-11 | criteria provided, single submitter | clinical testing | The c.6665C>T (p.A2222V) alteration is located in exon 15 (coding exon 15) of the PKD1 gene. This alteration results from a C to T substitution at nucleotide position 6665, causing the alanine (A) at amino acid position 2222 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Ce |
RCV001796750 | SCV004142860 | benign | not provided | 2023-09-01 | criteria provided, single submitter | clinical testing | PKD1: BP4, BS1, BS2 |
| Prevention |
RCV003942698 | SCV004771945 | likely benign | PKD1-related condition | 2019-12-26 | criteria provided, single submitter | clinical testing | This variant is classified as likely 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, |
RCV001292261 | SCV001480896 | likely benign | Polycystic kidney disease | no assertion criteria provided | clinical testing | The PKD1, p.Ala2222Val variant was not identified in the literature nor was it identified in the Clinvitae, ClinVar, GeneInsight COGR, PKD1-LOVD and PKD1-LOVD 3.0 databases. The variant was identified in dbSNP (ID: rs148496347) as “NA”, ADPKD Mutation Database (classified as likely neutral), the 1000 Genomes Project in 4 of 5000 chromosomes (frequency: 0.0008), the NHLBI GO Exome Sequencing Project in 14 of 8480 European American alleles, the Exome Aggregation Consortium database (March 14, 2016) in 49 of 106856 chromosomes (freq. 0.0005) in the following populations: European in 48 of 57726 chromosomes (freq. 0.0008), African in 1 of 7870 chromosomes (freq. 0.0001), but was not seen in Asian, Finish, Latino and Other populations, increasing the likelihood that this may be a low frequency benign variant in certain populations of origin. 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.Ala2222 residue is conserved across mammals and other organisms, however computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest that the variant may impact the protein; this information is not predictive enough to assume pathogenicity. The variant occurs outside of the splicing consensus sequence and 2 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. 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. | |
| Genome Diagnostics Laboratory, |
RCV000516393 | SCV002034247 | benign | not specified | no assertion criteria provided | clinical testing | ||
| Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV001796750 | SCV002038131 | likely benign | not provided | no assertion criteria provided | clinical testing |