ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.49G>T (p.Ala17Ser)

gnomAD frequency: 0.00005  dbSNP: rs149293970
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV001160294 SCV001322084 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 RCV001160294 SCV001564098 uncertain significance Autosomal recessive polycystic kidney disease 2021-08-24 criteria provided, single submitter clinical testing This sequence change replaces alanine with serine at codon 17 of the PKHD1 protein (p.Ala17Ser). The alanine residue is moderately conserved and there is a moderate physicochemical difference between alanine and serine. This variant is present in population databases (rs149293970, ExAC 0.02%). This variant has not been reported in the literature in individuals affected with PKHD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 909295). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PKHD1 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Fulgent Genetics, Fulgent Genetics RCV002483907 SCV002785719 uncertain significance Polycystic kidney disease 4 2021-12-24 criteria provided, single submitter clinical testing
Preventiongenetics, part of Exact Sciences RCV003433059 SCV004118040 uncertain significance PKHD1-related condition 2022-12-08 criteria provided, single submitter clinical testing The PKHD1 c.49G>T variant is predicted to result in the amino acid substitution p.Ala17Ser. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.024% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/6-51949683-C-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Natera, Inc. RCV001160294 SCV002083431 uncertain significance Autosomal recessive polycystic kidney disease 2018-07-25 no assertion criteria provided clinical testing

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