rs370487077
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The NM_001242896.3(DEPDC5):c.2486C>T(p.Pro829Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,613,938 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. P829P) has been classified as Likely benign.
Frequency
Consequence
NM_001242896.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DEPDC5 | NM_001242896.3 | c.2486C>T | p.Pro829Leu | missense_variant | 27/43 | ENST00000651528.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DEPDC5 | ENST00000651528.2 | c.2486C>T | p.Pro829Leu | missense_variant | 27/43 | NM_001242896.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152162Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000281 AC: 7AN: 249436Hom.: 0 AF XY: 0.0000296 AC XY: 4AN XY: 135312
GnomAD4 exome AF: 0.0000178 AC: 26AN: 1461776Hom.: 0 Cov.: 30 AF XY: 0.0000151 AC XY: 11AN XY: 727196
GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152162Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74334
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 28, 2023 | The c.2486C>T (p.P829L) alteration is located in exon 27 (coding exon 26) of the DEPDC5 gene. This alteration results from a C to T substitution at nucleotide position 2486, causing the proline (P) at amino acid position 829 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
See cases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein | Feb 19, 2021 | ACMG classification criteria: PM2, BP4 - |
Familial focal epilepsy with variable foci Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 829 of the DEPDC5 protein (p.Pro829Leu). This variant is present in population databases (rs370487077, gnomAD 0.01%). 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: 534795). 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