Submissions for variant NM_001378615.1(CC2D2A):c.1837G>A (p.Glu613Lys)

gnomAD frequency: 0.00010  dbSNP: rs201439617

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000724892	SCV000226585	uncertain significance	not provided	2018-07-19	criteria provided, single submitter	clinical testing
GeneDx	RCV000724892	SCV000329211	uncertain significance	not provided	2016-05-18	criteria provided, single submitter	clinical testing	The E613K variant in the E613K gene has not been published as a pathogenic variant, nor has it been reported as a benign polymorphism to our knowledge. The E613K variant was not observed with any significant frequency in approximately 6200 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The E613K 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 not conserved across species. In silico analysis predicts this variant likely does not alter the protein structure/function. We interpret E613K as a variant of unknown significance.
Fulgent Genetics, Fulgent Genetics	RCV000765755	SCV000897143	uncertain significance	COACH syndrome 1; Meckel syndrome, type 6; Joubert syndrome 9	2018-10-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001147083	SCV001307861	uncertain significance	Meckel syndrome, type 6	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.
Illumina Laboratory Services, Illumina	RCV001147084	SCV001307862	uncertain significance	Joubert syndrome 9	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.
Baylor Genetics	RCV001147084	SCV001521081	uncertain significance	Joubert syndrome 9	2019-08-08	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Labcorp Genetics (formerly Invitae), Labcorp	RCV001479910	SCV001684217	likely benign	Familial aplasia of the vermis; Meckel-Gruber syndrome	2025-01-06	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV004020077	SCV004920445	uncertain significance	Inborn genetic diseases	2022-03-22	criteria provided, single submitter	clinical testing	The c.1837G>A (p.E613K) alteration is located in exon 17 (coding exon 15) of the CC2D2A gene. This alteration results from a G to A substitution at nucleotide position 1837, causing the glutamic acid (E) at amino acid position 613 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.