Submissions for variant NM_138694.4(PKHD1):c.6184C>T (p.Leu2062=)

gnomAD frequency: 0.00271  dbSNP: rs116156469

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV000243100	SCV000315817	likely benign	not specified		criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000243100	SCV000702215	benign	not specified	2016-09-26	criteria provided, single submitter	clinical testing
Invitae	RCV000861149	SCV001001382	benign	Autosomal recessive polycystic kidney disease	2024-01-31	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000243100	SCV001448394	likely benign	not specified	2020-11-01	criteria provided, single submitter	clinical testing
GeneDx	RCV001589289	SCV001824645	likely benign	not provided	2020-11-18	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001292265	SCV001480924	likely benign	Polycystic kidney disease		no assertion criteria provided	clinical testing	The PKHD1 p.Leu2062= variant was not identified in the literature nor was it identified in the LOVD 3.0, RWTH AAachen University ARPKD databases. The variant was identified in dbSNP (ID: rs116156469) as “With Likely benign allele”, ClinVar (as likely benign by Prevention Genetics), and Clinvitae (1x as “likely benign”). The variant was identified in control databases in 381 of 276812 chromosomes at a frequency of 0.001376 in the following populations: African in 212 (2 homozygous) of 24028 chromosomes (freq. 0.0088), Ashkenazi Jewish in 46 of 10140 chromosomes (freq. 0.0045), South Asian in 78 (2 homozygous) of 30782 chromosomes (freq. 0.0025), Other in 9 of 6456 chromosomes (freq. 0.001), Latino in 21 of 34338 chromosomes (freq. 0.0006), and European (Non-Finnish) in 15 of 126444 chromosomes (freq. 0.0001) increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Consortium Feb 27, 2017). The p.Leu2062= 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.
Natera, Inc.	RCV000861149	SCV002078057	benign	Autosomal recessive polycystic kidney disease	2017-05-11	no assertion criteria provided	clinical testing