rs779428450

Variant names:

• chr22-31822720-C-G
• NM_001242896.3:c.2034C>G

Your query was ambiguous. Multiple possible variants found:

• chr22-31822720-C-G
• chr22-31822720-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001242896.3(DEPDC5):​c.2034C>G​(p.Asp678Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DEPDC5 NM_001242896.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.936

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]

ENSG00000285404 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEPDC5	NM_001242896.3	c.2034C>G	p.Asp678Glu	missense_variant	Exon 24 of 43	ENST00000651528.2	NP_001229825.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DEPDC5	ENST00000651528.2	c.2034C>G	p.Asp678Glu	missense_variant	Exon 24 of 43		NM_001242896.3	ENSP00000498382.1
ENSG00000285404	ENST00000646701.1	c.1786+3495C>G		intron_variant	Intron 20 of 20			ENSP00000496158.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461804 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727194

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.012	.;.;.;.;T;.;.;.;T;.;.;.;.
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.18
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.81	T;T;T;T;T;.;T;T;.;T;.;T;T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.066	T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.20	.;N;N;.;N;N;N;.;N;.;N;N;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	0.020	.;.;.;.;N;N;.;.;N;.;N;N;.
REVEL	Benign	0.075
Sift	Benign	0.29	.;.;.;.;T;T;.;.;T;.;T;T;.
Sift4G	Benign	0.83	.;.;.;.;T;T;.;.;T;.;T;T;.
Polyphen		0.0020	.;.;B;.;B;.;.;.;B;.;B;.;.
Vest4		0.43, 0.42, 0.30, 0.35
MutPred		0.14		Gain of phosphorylation at S681 (P = 0.1585);Gain of phosphorylation at S681 (P = 0.1585);Gain of phosphorylation at S681 (P = 0.1585);.;Gain of phosphorylation at S681 (P = 0.1585);Gain of phosphorylation at S681 (P = 0.1585);Gain of phosphorylation at S681 (P = 0.1585);.;Gain of phosphorylation at S681 (P = 0.1585);Gain of phosphorylation at S681 (P = 0.1585);Gain of phosphorylation at S681 (P = 0.1585);Gain of phosphorylation at S681 (P = 0.1585);.;
MVP		0.15
MPC		0.38
ClinPred		0.39	T
GERP RS		2.0
Varity_R		0.13

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.38		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.38		Position offset: -27

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-32218706;