rs765244692
Variant summary
Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2
The NM_001242896.3(DEPDC5):c.4136C>A(p.Ser1379Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000616 in 1,461,734 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. S1379C) has been classified as Uncertain significance.
Frequency
Consequence
NM_001242896.3 missense
Scores
Clinical Significance
Conservation
Publications
- epilepsy, familial focal, with variable foci 1Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Ambry Genetics, Illumina, G2P
- focal epilepsyInheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
- autosomal dominant epilepsy with auditory featuresInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- autosomal dominant nocturnal frontal lobe epilepsyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- familial focal epilepsy with variable fociInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- Brugada syndromeInheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
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ACMG classification
Our verdict: Likely_benign. The variant received -5 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DEPDC5 | ENST00000651528.2 | c.4136C>A | p.Ser1379Tyr | missense_variant | Exon 39 of 43 | NM_001242896.3 | ENSP00000498382.1 | |||
ENSG00000285404 | ENST00000646701.1 | c.1787-62455C>A | intron_variant | Intron 20 of 20 | ENSP00000496158.1 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD2 exomes AF: 0.0000281 AC: 7AN: 249112 AF XY: 0.0000148 show subpopulations
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461734Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3AN XY: 727164 show subpopulations
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
Familial focal epilepsy with variable foci Uncertain:1
This sequence change replaces serine, which is neutral and polar, with tyrosine, which is neutral and polar, at codon 1379 of the DEPDC5 protein (p.Ser1379Tyr). This variant is present in population databases (rs765244692, 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: 466490). 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