ClinVar Miner

Submissions for variant NM_017882.3(CLN6):c.5A>G (p.Glu2Gly) (rs3743088)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000187109 SCV000240684 uncertain significance not provided 2018-07-25 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the CLN6 gene. The E2G variant has beenreported previously in the homozygous state in an individual with late-infantile neuronal ceroidlipofuscinosis (Di Fruscio et al., 2015). The E2G variant is observed in 13/1008 (1.3%) alleles from individuals of East Asian background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015;Exome Variant Server). The E2G 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. Additionally, this substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Furthermore, missense variants in nearby residues (R5W, R6T) have been reported in the Human GeneMutation Database in association with NCL (Stenson et al., 2014). Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV001082320 SCV000628980 benign Neuronal ceroid lipofuscinosis 2020-12-08 criteria provided, single submitter clinical testing
Counsyl RCV000664477 SCV000788440 uncertain significance Neuronal ceroid lipofuscinosis 6 2017-01-25 criteria provided, single submitter clinical testing
Ambry Genetics RCV000715755 SCV000846586 uncertain significance Seizures 2019-03-26 criteria provided, single submitter clinical testing The p.E2G variant (also known as c.5A>G), located in coding exon 1 of the CLN6 gene, results from an A to G substitution at nucleotide position 5. The glutamic acid at codon 2 is replaced by glycine, an amino acid with similar properties. This variant was reported as homozygous in an individual with neuronal ceroid lipofuscinosis (Di Fruscio G et al. Autophagy, 2015;11:928-38). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Illumina Clinical Services Laboratory,Illumina RCV001082320 SCV001278036 likely benign Neuronal ceroid lipofuscinosis 2017-08-08 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). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Mayo Clinic Laboratories, Mayo Clinic RCV000187109 SCV001713715 uncertain significance not provided 2021-01-12 criteria provided, single submitter clinical testing

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