ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.5896C>T (p.Leu1966=)

gnomAD frequency: 0.03202  dbSNP: rs1266923
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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000082564 SCV000114606 benign not specified 2013-04-23 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV000082564 SCV000315815 benign not specified criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000314583 SCV000464077 benign Autosomal recessive polycystic kidney disease 2018-01-12 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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000589675 SCV000699870 benign not provided 2016-04-27 criteria provided, single submitter clinical testing Variant summary: The c.5896C>T variant involves the alteration of a conserved nucleotide resulting in a synonymous change. 4/5 in silico tools via Alamut predict no significant effect on splicing. The variant was observed in the large and broad cohorts of the ExAC project at an allele frequency of 3.2%, predominantly observed in the African subpopulation at a frequency of 13.5% including 82 homozygous occurrences. This frequency exceeds the maximal expected allele frequency for a pathogenic variant in PKHD1 (0.71%), suggesting this is a benign polymorphism found primarily in population(s) of African origin. Publications and a clinical lab have classifed the variant as polymorphism/benign.
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000314583 SCV000743914 benign Autosomal recessive polycystic kidney disease 2014-12-01 criteria provided, single submitter clinical testing
Invitae RCV000314583 SCV000754662 benign Autosomal recessive polycystic kidney disease 2024-02-01 criteria provided, single submitter clinical testing
Pars Genome Lab RCV001530422 SCV001745243 benign Polycystic kidney disease 4 2021-06-19 criteria provided, single submitter clinical testing
GeneDx RCV000589675 SCV001751499 benign not provided 2018-07-09 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System RCV001291855 SCV000592898 benign Polycystic kidney disease no assertion criteria provided clinical testing The PKHD1 p.Leu1966Leu variant was identified in 2 of 726 proband chromosomes (frequency: 0.003) from individuals or families with ARPKD, and was present in 22 of 920 control chromosomes (frequency: 0.024) from healthy individuals (Bergmann 2005, Furu 2004, Losekoot 2005, Sharp 2005). The variant was also identified in dbSNP (ID: rs1266923) “With benign allele”, in 1000 Genomes Project in 408 of 5006 chromosomes (frequency: 0.0815), in NHLBI GO Exome Sequencing Project in 35 of 8600 (frequency: 0.004) European American and 586 in 4406 (frequency: 0.1285) African American alleles. This variant was identified in the Exome Aggregation Consortium database (March 14, 2016) in 3934 of 121262 chromosomes (frequency: 0.03) from a population (frequency) of African (0.14), East Asian (0.11), Finnish (0.06), South Asian (0.04), Other (0.03), Latino (0.02), and European Non-Finnish (0.006) individuals. Furthermore, the variant is listed in the ClinVar database as benign by Emory Genetics Laboratory, in the GeneInsight COGR database as benign by LMM, and in RWTH Aachen University ARPKD database as a polymorphism. The p.Leu1966Leu 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 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, this variant is classified as benign.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000314583 SCV000734506 benign Autosomal recessive polycystic kidney disease no assertion criteria provided clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV000082564 SCV002036226 benign not specified no assertion criteria provided clinical testing
Natera, Inc. RCV000314583 SCV002078063 benign Autosomal recessive polycystic kidney disease 2017-05-11 no assertion criteria provided clinical testing

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