Submissions for variant NM_001384732.1(CPLANE1):c.4643A>G (p.Asp1548Gly)

dbSNP: rs759649053

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Institute of Medical Genetics, University of Zurich	RCV000605589	SCV000579464	likely pathogenic	Joubert syndrome 17	2017-05-18	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004689763	SCV005185933	uncertain significance	not specified	2024-05-03	criteria provided, single submitter	clinical testing	Variant summary: CPLANE1 (alias C5ORF42) c.4643A>G (p.Asp1548Gly) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 250836 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.4643A>G has been reported in the literature in trans with a pathogenic variant in at least 1 individual affected with Joubert Syndrome And Related Disorders (example, Asadollahi_2018, Bonnard_2018). It was also found in the homozygous state in 1 individual undergoing genetic testing for a suspected neurological disorder (Ganapathy_2019) and in as an unspecfied genotype (i.e. zygosity unknown) in 1 individual with Joubert syndrome (Romani_2015). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 29321670, 29605658, 31069529, 25407461). ClinVar contains an entry for this variant (Variation ID: 427892). Based on the evidence outlined above, the variant was classified as uncertain significance.