Submissions for variant NM_138694.4(PKHD1):c.8286C>T (p.Asp2762=)

gnomAD frequency: 0.00004  dbSNP: rs749740610

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000874322	SCV001016480	likely benign	Autosomal recessive polycystic kidney disease	2024-03-02	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001579052	SCV001806444	likely benign	Polycystic kidney disease 4	2021-07-22	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV001579052	SCV002808825	likely benign	Polycystic kidney disease 4	2021-12-15	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001292263	SCV001480922	likely benign	Polycystic kidney disease		no assertion criteria provided	clinical testing	The PKHD1 p.Asp2762= variant was not identified in the literature nor was it identified in the ClinVar, GeneInsight-COGR, LOVD 3.0, RWTH AAachen University ARPKD, databases. The variant was identified in dbSNP (ID: rs749740610) as N/A, database. The variant was identified in control databases in 14 of 276862 chromosomes at a frequency of 0.000051 (Genome Aggregation Database Feb 27, 2017). Breakdown of the observations by population include African in 2 of 24024 chromosomes (freq: 0.000083), European Non-Finnish in 3 of 126532 chromosomes (freq: 0.000024), East Asian in 7 of 18830 chromosomes (freq: 0.000372), and South Asian in 2 of 30780 chromosomes (freq: 0.000065), while the variant was not observed in the Other, Latino, Ashkenazi Jewish, European Finnish, populations. The p.Asp2762= 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 addition, 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, 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.
PreventionGenetics, part of Exact Sciences	RCV003908306	SCV004721594	likely benign	PKHD1-related disorder	2021-01-20	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).