rs16989537
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1
The NM_001242896.3(DEPDC5):c.2241C>G(p.Leu747=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00616 in 1,614,154 control chromosomes in the GnomAD database, including 261 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.023 ( 119 hom., cov: 32)
Exomes 𝑓: 0.0044 ( 142 hom. )
Consequence
DEPDC5
NM_001242896.3 synonymous
NM_001242896.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.61
Genes affected
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.45).
BP6
?
Variant 22-31837042-C-G is Benign according to our data. Variant chr22-31837042-C-G is described in ClinVar as [Benign]. Clinvar id is 414452.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-31837042-C-G is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=1.61 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0709 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DEPDC5 | NM_001242896.3 | c.2241C>G | p.Leu747= | synonymous_variant | 26/43 | ENST00000651528.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DEPDC5 | ENST00000651528.2 | c.2241C>G | p.Leu747= | synonymous_variant | 26/43 | NM_001242896.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0227 AC: 3454AN: 152146Hom.: 121 Cov.: 32
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GnomAD3 exomes AF: 0.00864 AC: 2156AN: 249566Hom.: 57 AF XY: 0.00794 AC XY: 1075AN XY: 135394
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GnomAD4 exome AF: 0.00443 AC: 6480AN: 1461890Hom.: 142 Cov.: 34 AF XY: 0.00464 AC XY: 3373AN XY: 727246
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GnomAD4 genome ? AF: 0.0227 AC: 3464AN: 152264Hom.: 119 Cov.: 32 AF XY: 0.0229 AC XY: 1702AN XY: 74450
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 24, 2016 | 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 foci Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 27, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at