ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.7567A>G (p.Ile2523Val)

gnomAD frequency: 0.00006  dbSNP: rs146962673
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000728359 SCV000855918 uncertain significance not provided 2017-07-20 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002477683 SCV002788534 uncertain significance Polycystic kidney disease 4 2022-01-08 criteria provided, single submitter clinical testing
Invitae RCV002533090 SCV003490174 uncertain significance Autosomal recessive polycystic kidney disease 2021-12-26 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 2523 of the PKHD1 protein (p.Ile2523Val). This variant is present in population databases (rs146962673, gnomAD 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: 593347). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.
Ambry Genetics RCV002533091 SCV003752894 uncertain significance Inborn genetic diseases 2022-12-28 criteria provided, single submitter clinical testing The c.7567A>G (p.I2523V) alteration is located in exon 48 (coding exon 47) of the PKHD1 gene. This alteration results from a A to G substitution at nucleotide position 7567, causing the isoleucine (I) at amino acid position 2523 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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