ClinVar Miner

Submissions for variant NM_000297.4(PKD2):c.2420G>A (p.Arg807Gln) (rs147654263)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000204608 SCV000260370 benign Autosomal dominant polycystic kidney disease 2019-12-31 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000244886 SCV000303533 likely benign not specified criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001001908 SCV000451564 likely benign Polycystic kidney disease 2 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000434759 SCV000511521 benign not provided 2017-01-06 criteria provided, single submitter clinical testing
GeneDx RCV000244886 SCV000514123 likely benign not specified 2018-01-08 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000244886 SCV000708717 benign not specified 2017-06-20 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001001908 SCV001159661 benign Polycystic kidney disease 2 2018-12-30 criteria provided, single submitter clinical testing
Molecular Genetics of Inherited Kidney Disorders Laboratory,Garvan Institute of Medical Research RCV000204608 SCV001430171 likely benign Autosomal dominant polycystic kidney disease 2019-01-01 criteria provided, single submitter research
Athena Diagnostics Inc RCV000244886 SCV001475372 benign not specified 2019-10-22 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001292081 SCV001480821 benign Polycystic kidney disease no assertion criteria provided clinical testing The PKD2 p.Arg807Gln variant was identified in 6 of 3926 proband chromosomes (frequency: 0.002) from individuals or families with ADPKD (Magistroni 2003, Robinson 2012, Neumann 2013, Rossetti 2007, Rossetti 2012). The variant was also identified in the following databases: dbSNP (ID: rs147654263) as “With other allele”, ClinVar (classified as benign by Invitae and Children Mercy hospital; as likely benign by Prevention Genetics and Illumina; and as uncertain significance by GeneDx), LOVD 3.0 (1x, reported as "does not affect protein”), ADPKD Mutation Database (as likely neutral). The variant was not identified in PKD1-LOVD database. The variant was identified in control databases in 875 (4 homozygous) of 276852 chromosomes at a frequency of 0.003, increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Consortium Feb 27, 2017). The variant was observed in the following populations: African in 9 of 24032 chromosomes (freq. 0.0004), Other in 27 of 6462 chromosomes (freq. 0.004), Latino in 70 of 34396 chromosomes (freq. 0.002), European in 289 (1 homozygous) of 126416 chromosomes (freq. 0.002), Ashkenazi Jewish in 47 of 10138 chromosomes (freq. 0.005), East Asian in 1 of 18838 chromosomes (freq. 0.00005), Finnish in 431 (3 homozygous) of 25788 chromosomes (freq. 0.02), and South Asian in 1 of 30782 chromosomes (freq. 0.00003). The p.Arg807Gln residue is conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. A functional study showed R807Q had no effect on the coiled-coil domain; the variant was identified as likely polymorphism (Giamarchi 2010). In summary, based on the above information this variant meets our laboratory criteria to be classified as benign.

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