rs746372266
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The NM_001242896.3(DEPDC5):c.2465C>G(p.Pro822Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000109 in 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P822S) has been classified as Uncertain significance.
Frequency
Consequence
NM_001242896.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DEPDC5 | NM_001242896.3 | c.2465C>G | p.Pro822Arg | missense_variant | 27/43 | ENST00000651528.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DEPDC5 | ENST00000651528.2 | c.2465C>G | p.Pro822Arg | missense_variant | 27/43 | NM_001242896.3 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.0000281 AC: 7AN: 249506Hom.: 0 AF XY: 0.0000369 AC XY: 5AN XY: 135356
GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461868Hom.: 0 Cov.: 30 AF XY: 0.0000110 AC XY: 8AN XY: 727236
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 04, 2024 | The c.2465C>G (p.P822R) alteration is located in exon 27 (coding exon 26) of the DEPDC5 gene. This alteration results from a C to G substitution at nucleotide position 2465, causing the proline (P) at amino acid position 822 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Familial focal epilepsy with variable foci Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 17, 2023 | This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 822 of the DEPDC5 protein (p.Pro822Arg). This variant is present in population databases (rs746372266, gnomAD 0.02%). 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: 534802). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at