Submissions for variant NM_201548.5(CERKL):c.157G>A (p.Glu53Lys)

gnomAD frequency: 0.00238  dbSNP: rs141389059

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000419430	SCV000536400	uncertain significance	not provided	2017-01-24	criteria provided, single submitter	clinical testing	The E53K variant in the CERKL gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. Although not observed in the homozygous state, the NHLBI ESP Exome Sequencing Project reports E53K was observed in 21/8598 (0.24%) alleles from individuals of Eastern European background, indicating it may be a rare variant in this population. The E53K variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in mammals. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret E53K as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000419430	SCV001023134	benign	not provided	2025-01-29	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001138252	SCV001298290	uncertain significance	Retinitis pigmentosa	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Natera, Inc.	RCV001271350	SCV001452437	likely benign	Retinitis pigmentosa 26	2020-06-06	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004755919	SCV005344510	benign	CERKL-related disorder	2024-09-19	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).