ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.1877A>G (p.Lys626Arg)

gnomAD frequency: 0.00080  dbSNP: rs117122807
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169041 SCV000220199 benign Autosomal recessive polycystic kidney disease 2014-03-27 criteria provided, single submitter literature only
Eurofins Ntd Llc (ga) RCV000176125 SCV000227727 benign not specified 2015-04-15 criteria provided, single submitter clinical testing
Invitae RCV000169041 SCV000557647 benign Autosomal recessive polycystic kidney disease 2024-01-31 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000169041 SCV001325837 likely benign Autosomal recessive polycystic kidney disease 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.
GeneDx RCV001706102 SCV001873583 benign not provided 2020-04-15 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 30566001, 28814334, 28578020, 21790888)
Department of Pathology and Laboratory Medicine, Sinai Health System RCV001292486 SCV001481079 likely benign Polycystic kidney disease no assertion criteria provided clinical testing The PKHD1 p.Lys626Arg variant was identified in the literature in a case report of a 22 week fetus with findings consistent with ARPKD. Fetal genetic testing was declined, however the father was identified to carry the p.Lys626Arg variant but no additional suspicious variants were identified in the mother or father (Jang 2011). The variant was also identified in dbSNP (ID: rs117122807) “With Benign allele”, ClinVar (classified as benign by Counsyl and Emory Genetics), LOVD 3.0 (unclassified), and the RWTH AAachen University ARPKD database (unclassified) databases, but was not in the Geneinsight-COGR database. The variant was identified in control databases in 734 of 277024 chromosomes (10 homozygous) at a frequency of 0.00265 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Consortium Feb 27, 2017). The p.Lys626Arg residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out 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. 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.
Natera, Inc. RCV000169041 SCV002081059 benign Autosomal recessive polycystic kidney disease 2017-05-11 no assertion criteria provided clinical testing

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