Genetic Variant DEPDC1:p.Arg808Leu (chr1-68476945-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001114120.3(DEPDC1):c.2423G>T(p.Arg808Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000015 in 1,595,354 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

DEPDC1
NM_001114120.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.484

Publications

0 publications found

Variant links:

Genes affected

DEPDC1 (HGNC:22949): (DEP domain containing 1) Predicted to enable GTPase activator activity. Involved in negative regulation of transcription, DNA-templated. Located in nucleus. Part of transcription repressor complex. [provided by Alliance of Genome Resources, Apr 2022]

DEPDC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10019925).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001114120.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEPDC1	NM_001114120.3	MANE Select	c.2423G>T	p.Arg808Leu	missense	Exon 12 of 12	NP_001107592.1	Q5TB30-5
	DEPDC1	NM_017779.6		c.1571G>T	p.Arg524Leu	missense	Exon 11 of 11	NP_060249.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DEPDC1	ENST00000456315.7	TSL:1 MANE Select	c.2423G>T	p.Arg808Leu	missense	Exon 12 of 12	ENSP00000412292.2	Q5TB30-5
DEPDC1	ENST00000370966.9	TSL:1	c.1571G>T	p.Arg524Leu	missense	Exon 11 of 11	ENSP00000360005.5	Q5TB30-2
DEPDC1	ENST00000489862.1	TSL:1	n.*640G>T		non_coding_transcript_exon	Exon 13 of 13	ENSP00000436464.1	H0YES2

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151746

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000841

AC:

AN:

237692

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000186

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000159

AC:

AN:

1443608

Hom.:

Cov.:

AF XY:

0.0000125

AC XY:

AN XY:

717296

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32816

American (AMR)

AF:

0.00

AC:

AN:

43048

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25666

East Asian (EAS)

AF:

0.00

AC:

AN:

39126

South Asian (SAS)

AF:

0.00

AC:

AN:

82918

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52866

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4134

European-Non Finnish (NFE)

AF:

0.0000199

AC:

AN:

1103550

Other (OTH)

AF:

0.0000168

AC:

AN:

59484

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000659

AC:

AN:

151746

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74078

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

41384

American (AMR)

AF:

0.00

AC:

AN:

15190

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10588

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

67796

Other (OTH)

AF:

0.00

AC:

AN:

2086

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000825

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.085

FATHMM_MKL

Benign

0.73

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.016

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PhyloP100

0.48

PrimateAI

Benign

0.23

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.091

Sift

Benign

0.086

Sift4G

Benign

0.17

Polyphen

0.44

Vest4

0.30

MutPred

0.31

Loss of solvent accessibility (P = 0.0052)

MVP

0.36

MPC

0.36

ClinPred

0.28

GERP RS

3.5

Varity_R

0.10

gMVP

0.29

Mutation Taster

=88/12

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over