Genetic Variant DEPDC1:c.769+52_769+55dupGTGT (chr1-68486881-A-AACAC) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001114120.3(DEPDC1):c.769+52_769+55dupGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00624 in 1,175,208 control chromosomes in the GnomAD database, including 12 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.011 ( 10 hom., cov: 0)

Exomes 𝑓: 0.0056 ( 2 hom. )

Consequence

DEPDC1
NM_001114120.3 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.54

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: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

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.769+52_769+55dupGTGT		intron	N/A	NP_001107592.1	Q5TB30-5
	DEPDC1	NM_017779.6		c.769+52_769+55dupGTGT		intron	N/A	NP_060249.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DEPDC1	ENST00000456315.7	TSL:1 MANE Select	c.769+55_769+56insGTGT	intron	N/A	ENSP00000412292.2	Q5TB30-5
DEPDC1	ENST00000370966.9	TSL:1	c.769+55_769+56insGTGT	intron	N/A	ENSP00000360005.5	Q5TB30-2
DEPDC1	ENST00000489862.1	TSL:1	n.472+55_472+56insGTGT	intron	N/A	ENSP00000436464.1	H0YES2

Frequencies

GnomAD3 genomes

AF:

0.0106

AC:

1529

AN:

143624

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0130

Gnomad AMI

AF:

0.0594

Gnomad AMR

AF:

0.00628

Gnomad ASJ

AF:

0.0149

Gnomad EAS

AF:

0.0140

Gnomad SAS

AF:

0.00775

Gnomad FIN

AF:

0.00720

Gnomad MID

AF:

0.00327

Gnomad NFE

AF:

0.00978

Gnomad OTH

AF:

0.0107

GnomAD4 exome

AF:

0.00563

AC:

5808

AN:

1031492

Hom.:

AF XY:

0.00575

AC XY:

2902

AN XY:

504426

show subpopulations

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

African (AFR)

AF:

0.00803

AC:

181

AN:

22540

American (AMR)

AF:

0.00564

AC:

101

AN:

17916

Ashkenazi Jewish (ASJ)

AF:

0.0110

AC:

169

AN:

15396

East Asian (EAS)

AF:

0.0103

AC:

312

AN:

30194

South Asian (SAS)

AF:

0.00461

AC:

139

AN:

30166

European-Finnish (FIN)

AF:

0.00808

AC:

334

AN:

41328

Middle Eastern (MID)

AF:

0.00635

AC:

AN:

3308

European-Non Finnish (NFE)

AF:

0.00521

AC:

4312

AN:

828408

Other (OTH)

AF:

0.00566

AC:

239

AN:

42236

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 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: 0.328

Heterozygous variant carriers

364

728

1092

1456

1820

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

172

344

516

688

860

<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:

0.0106

AC:

1529

AN:

143716

Hom.:

Cov.:

AF XY:

0.0104

AC XY:

721

AN XY:

69594

show subpopulations

African (AFR)

AF:

0.0130

AC:

505

AN:

38944

American (AMR)

AF:

0.00627

AC:

AN:

14186

Ashkenazi Jewish (ASJ)

AF:

0.0149

AC:

AN:

3350

East Asian (EAS)

AF:

0.0140

AC:

AN:

4840

South Asian (SAS)

AF:

0.00776

AC:

AN:

4380

European-Finnish (FIN)

AF:

0.00720

AC:

AN:

9446

Middle Eastern (MID)

AF:

0.00350

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.00978

AC:

640

AN:

65414

Other (OTH)

AF:

0.0106

AC:

AN:

1978

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

131

196

262

327

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<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:

0.00494

Hom.:

278

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.5

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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