Submissions for variant NM_001242896.3(DEPDC5):c.2288G>T (p.Arg763Leu)

dbSNP: rs542384516

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001211815	SCV001383374	uncertain significance	Familial focal epilepsy with variable foci	2023-12-04	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 763 of the DEPDC5 protein (p.Arg763Leu). This variant is present in population databases (rs542384516, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with DEPDC5-related conditions. ClinVar contains an entry for this variant (Variation ID: 941938). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx	RCV003235498	SCV003933092	uncertain significance	not provided	2022-12-16	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics	RCV003246760	SCV003952078	uncertain significance	Inborn genetic diseases	2023-05-08	criteria provided, single submitter	clinical testing	The c.2288G>T (p.R763L) alteration is located in exon 26 (coding exon 25) of the DEPDC5 gene. This alteration results from a G to T substitution at nucleotide position 2288, causing the arginine (R) at amino acid position 763 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003387975	SCV004099863	uncertain significance	not specified	2023-09-15	criteria provided, single submitter	clinical testing	Variant summary: DEPDC5 c.2288G>T (p.Arg763Leu) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 249502 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.2288G>T in individuals affected with DEPDC5-related conditions and no experimental evidence demonstrating its impact on protein function have been reported. Three submitters have cited clinical-significance assessments for this variant to ClinVar after 2014, and all submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.