rs746913609
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6_ModerateBS1
The NM_001242896.3(DEPDC5):c.2171-10C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000304 in 1,546,022 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 Likely benign (★).
Frequency
Genomes: 𝑓 0.000040 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000029 ( 0 hom. )
Consequence
DEPDC5
NM_001242896.3 splice_polypyrimidine_tract, intron
NM_001242896.3 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.0001130
1
Clinical Significance
Conservation
PhyloP100: 0.454
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 -8 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.66).
BP6
?
Variant 22-31836962-C-T is Benign according to our data. Variant chr22-31836962-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 466465.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0000294 (41/1395324) while in subpopulation MID AF= 0.00224 (12/5358). AF 95% confidence interval is 0.00129. There are 0 homozygotes in gnomad4_exome. There are 17 alleles in male gnomad4_exome subpopulation. Median coverage is 34. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DEPDC5 | NM_001242896.3 | c.2171-10C>T | splice_polypyrimidine_tract_variant, intron_variant | ENST00000651528.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DEPDC5 | ENST00000651528.2 | c.2171-10C>T | splice_polypyrimidine_tract_variant, intron_variant | NM_001242896.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000398 AC: 6AN: 150698Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000203 AC: 5AN: 246754Hom.: 0 AF XY: 0.0000224 AC XY: 3AN XY: 133892
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GnomAD4 exome AF: 0.0000294 AC: 41AN: 1395324Hom.: 0 Cov.: 34 AF XY: 0.0000245 AC XY: 17AN XY: 693430
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GnomAD4 genome ? AF: 0.0000398 AC: 6AN: 150698Hom.: 0 Cov.: 32 AF XY: 0.0000679 AC XY: 5AN XY: 73608
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Familial focal epilepsy with variable foci Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jul 25, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Calibrated prediction
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dbscSNV1_ADA
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at