rs202083639
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 3P and 7B. PM2PP2BP4_ModerateBP6BS1
The NM_001242896.3(DEPDC5):c.1525C>T(p.Arg509Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000672 in 1,614,028 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R509H) has been classified as Likely benign.
Frequency
Consequence
NM_001242896.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DEPDC5 | NM_001242896.3 | c.1525C>T | p.Arg509Cys | missense_variant | 21/43 | ENST00000651528.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DEPDC5 | ENST00000651528.2 | c.1525C>T | p.Arg509Cys | missense_variant | 21/43 | NM_001242896.3 | P4 |
Frequencies
GnomAD3 genomes AF: 0.000440 AC: 67AN: 152140Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000325 AC: 81AN: 249552Hom.: 0 AF XY: 0.000369 AC XY: 50AN XY: 135384
GnomAD4 exome AF: 0.000696 AC: 1018AN: 1461888Hom.: 0 Cov.: 31 AF XY: 0.000652 AC XY: 474AN XY: 727246
GnomAD4 genome AF: 0.000440 AC: 67AN: 152140Hom.: 0 Cov.: 32 AF XY: 0.000444 AC XY: 33AN XY: 74340
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:2
Uncertain significance, criteria provided, single submitter | clinical testing | Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden | Nov 03, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2023 | DEPDC5: BP4, BS1:Supporting, BS2 - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jun 19, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 06, 2020 | - - |
Epilepsy, familial focal, with variable foci 1 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago | Mar 30, 2021 | DEPDC5 NM_001242896.1 exon 21 p.Arg509Cys (c.1525C>T): This variant has not been reported in the literature but is present in 0.09% (63/64570) of European alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/22-31815071-C-T?dataset=gnomad_r3). This variant is present in ClinVar (Variation ID:420430); of note, one submitter in ClinVar identifies at least one non-segregation for this variant within their internal databases. Evolutionary conservation suggests that this variant may not impact the protein; computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 25, 2019 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Familial focal epilepsy with variable foci Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
DEPDC5-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 08, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at