ClinVar Miner

Submissions for variant NM_000297.4(PKD2):c.2134T>C (p.Leu712=)

gnomAD frequency: 0.00563  dbSNP: rs73841280
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000654892 SCV000776796 benign Autosomal dominant polycystic kidney disease 2024-01-31 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV001155472 SCV001316899 likely benign Polycystic kidney disease 2 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Athena Diagnostics RCV001288348 SCV001475371 benign not specified 2020-09-11 criteria provided, single submitter clinical testing
GeneDx RCV001576460 SCV001803656 likely benign not provided 2021-04-09 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System RCV001292307 SCV001481072 likely benign Polycystic kidney disease no assertion criteria provided clinical testing The PKD2 p.Leu712Leu variant was not identified in the literature nor was it identified in the ClinVar, Genesight-COGR, LOVD 3.0, PKD1-LOVD, databases. The variant was identified in dbSNP (ID: rs73841280) with ”NA”, in ADPKD Mutation Database (2x, as likely neutral, and rare). The variant was identified in control databases in 482 of 277054 chromosomes at a frequency of 0.00174 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Consortium Feb 27, 2017)". The variant was identified in the following population at a frequency greater than 1%: African in 440 of 24026 chromosomes (freq: 0.018). In addition we cannot be certain that data from control databases is specific to PKD1 and not from one of the six PKD1 pseudogenes. The variant p.Leu712Leu 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 addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. A co-occurring likely pathogenic PKD1 variant [c.6916-9G>A, r.(spl?)] was identified in 1 individual with ADPKD in our laboratory, increasing the likelihood that p.Leu712Leu variant does not have clinical significance. 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.

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