Our verdict is Benign. The variant received -15 ACMG points: 1P and 16B. PP3BP4_StrongBP6_Very_StrongBS2
The NM_001242896.3(DEPDC5):c.161A>C(p.Gln54Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000204 in 1,613,114 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 Benign (★★).
DEPDC5 (HGNC:18423): (DEP domain containing 5, GATOR1 subcomplex subunit) This gene encodes a member of the IML1 family of proteins involved in G-protein signaling pathways. The mechanistic target of rapamycin complex 1 (mTORC1) pathway regulates cell growth by sensing the availability of nutrients. The protein encoded by this gene is a component of the GATOR1 (GAP activity toward Rags) complex which inhibits the amino acid-sensing branch of the mTORC1 pathway. Mutations in this gene are associated with autosomal dominant familial focal epilepsy with variable foci. A single nucleotide polymorphism in an intron of this gene has been associated with an increased risk of hepatocellular carcinoma in individuals with chronic hepatitis C virus infection. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]
DEPDC5 Gene-Disease associations (from GenCC):
epilepsy, familial focal, with variable foci 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Ambry Genetics, Illumina, G2P
focal epilepsy
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
autosomal dominant epilepsy with auditory features
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Our verdict: Benign. The variant received -15 ACMG points.
PP3
Multiple lines of computational evidence support a deleterious effect 7: AlphaMissense, BayesDel_noAF, Cadd, FATHMM_MKL, phyloP100way_vertebrate, PrimateAI, PROVEAN [when max_spliceai, MetaRNN, MutationTaster was below the threshold]
BP4
Computational evidence support a benign effect (MetaRNN=0.022509992).
BP6
Variant 22-31760670-A-C is Benign according to our data. Variant chr22-31760670-A-C is described in CliVar as Benign. Clinvar id is 264749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-31760670-A-C is described in CliVar as Benign. Clinvar id is 264749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-31760670-A-C is described in CliVar as Benign. Clinvar id is 264749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-31760670-A-C is described in CliVar as Benign. Clinvar id is 264749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-31760670-A-C is described in CliVar as Benign. Clinvar id is 264749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-31760670-A-C is described in CliVar as Benign. Clinvar id is 264749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-31760670-A-C is described in CliVar as Benign. Clinvar id is 264749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-31760670-A-C is described in CliVar as Benign. Clinvar id is 264749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-31760670-A-C is described in CliVar as Benign. Clinvar id is 264749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-31760670-A-C is described in CliVar as Benign. Clinvar id is 264749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-31760670-A-C is described in CliVar as Benign. Clinvar id is 264749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-31760670-A-C is described in CliVar as Benign. Clinvar id is 264749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-31760670-A-C is described in CliVar as Benign. Clinvar id is 264749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-31760670-A-C is described in CliVar as Benign. Clinvar id is 264749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-31760670-A-C is described in CliVar as Benign. Clinvar id is 264749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-31760670-A-C is described in CliVar as Benign. Clinvar id is 264749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-31760670-A-C is described in CliVar as Benign. Clinvar id is 264749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-31760670-A-C is described in CliVar as Benign. Clinvar id is 264749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-31760670-A-C is described in CliVar as Benign. Clinvar id is 264749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-31760670-A-C is described in CliVar as Benign. Clinvar id is 264749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-31760670-A-C is described in CliVar as Benign. Clinvar id is 264749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-31760670-A-C is described in CliVar as Benign. Clinvar id is 264749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-31760670-A-C is described in CliVar as Benign. Clinvar id is 264749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-31760670-A-C is described in CliVar as Benign. Clinvar id is 264749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-31760670-A-C is described in CliVar as Benign. Clinvar id is 264749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-31760670-A-C is described in CliVar as Benign. Clinvar id is 264749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-31760670-A-C is described in CliVar as Benign. Clinvar id is 264749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-31760670-A-C is described in CliVar as Benign. Clinvar id is 264749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-31760670-A-C is described in CliVar as Benign. Clinvar id is 264749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-31760670-A-C is described in CliVar as Benign. Clinvar id is 264749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-31760670-A-C is described in CliVar as Benign. Clinvar id is 264749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-31760670-A-C is described in CliVar as Benign. Clinvar id is 264749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-31760670-A-C is described in CliVar as Benign. Clinvar id is 264749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-31760670-A-C is described in CliVar as Benign. Clinvar id is 264749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-31760670-A-C is described in CliVar as Benign. Clinvar id is 264749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-31760670-A-C is described in CliVar as Benign. Clinvar id is 264749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-31760670-A-C is described in CliVar as Benign. Clinvar id is 264749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-31760670-A-C is described in CliVar as Benign. Clinvar id is 264749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-31760670-A-C is described in CliVar as Benign. Clinvar id is 264749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-31760670-A-C is described in CliVar as Benign. Clinvar id is 264749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-31760670-A-C is described in CliVar as Benign. Clinvar id is 264749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-31760670-A-C is described in CliVar as Benign. Clinvar id is 264749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-31760670-A-C is described in CliVar as Benign. Clinvar id is 264749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-31760670-A-C is described in CliVar as Benign. Clinvar id is 264749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-31760670-A-C is described in CliVar as Benign. Clinvar id is 264749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-31760670-A-C is described in CliVar as Benign. Clinvar id is 264749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-31760670-A-C is described in CliVar as Benign. Clinvar id is 264749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-31760670-A-C is described in CliVar as Benign. Clinvar id is 264749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-31760670-A-C is described in CliVar as Benign. Clinvar id is 264749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-31760670-A-C is described in CliVar as Benign. Clinvar id is 264749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Epilepsy, familial focal, with variable foci 1Uncertain:1Other:1
Feb 19, 2021
New York Genome Center
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
-
GeneReviews
Significance:not provided
Review Status:no classification provided
Collection Method:literature only
- -
not providedBenign:2
Jan 22, 2020
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
This variant is associated with the following publications: (PMID: 26505888, 30093711) -
Apr 27, 2018
Athena Diagnostics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Inborn genetic diseasesBenign:1
Jul 23, 2019
Ambry Genetics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
This alteration is classified as 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 fociBenign:1
Oct 24, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
DEPDC5-related disorderBenign:1
Apr 08, 2021
PreventionGenetics, part of Exact Sciences
Significance:Likely benign
Review Status:no assertion criteria provided
Collection Method:clinical testing
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). -