ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.11507-11C>T

gnomAD frequency: 0.00050  dbSNP: rs201478327
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000586413 SCV000699845 uncertain significance not specified 2020-08-10 criteria provided, single submitter clinical testing Variant summary: PKHD1 c.11507-11C>T alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00069 in 250504 control chromosomes, predominantly at a frequency of 0.0012 within the Non-Finnish European subpopulation in the gnomAD database. This frequency is not significantly higher than expected for a pathogenic variant in PKHD1 causing Polycystic Kidney and Hepatic Disease (0.00069 vs 0.0071), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.11507-11C>T in individuals affected with Polycystic Kidney and Hepatic Disease and no experimental evidence demonstrating its impact on protein function have been reported. One other ClinVar submitter (evaluation after 2014) cite the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly benign.
Illumina Laboratory Services, Illumina RCV001162834 SCV001324807 uncertain significance Autosomal recessive polycystic kidney disease 2018-01-13 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Invitae RCV001162834 SCV001702186 likely benign Autosomal recessive polycystic kidney disease 2024-01-24 criteria provided, single submitter clinical testing
GeneDx RCV001555004 SCV001776349 likely benign not provided 2021-05-16 criteria provided, single submitter clinical testing

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