Genetic Variant DEPDC1:c.769+46_769+55dupGTGTGTGTGT (chr1-68486881-A-AACACACACAC) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001114120.3(DEPDC1):c.769+46_769+55dupGTGTGTGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,177,342 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000070 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000015 ( 0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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+46_769+55dupGTGTGTGTGT		intron	N/A	NP_001107592.1	Q5TB30-5
	DEPDC1	NM_017779.6		c.769+46_769+55dupGTGTGTGTGT		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+56insGTGTGTGTGT	intron	N/A	ENSP00000412292.2	Q5TB30-5
DEPDC1	ENST00000370966.9	TSL:1	c.769+55_769+56insGTGTGTGTGT	intron	N/A	ENSP00000360005.5	Q5TB30-2
DEPDC1	ENST00000489862.1	TSL:1	n.472+55_472+56insGTGTGTGTGT	intron	N/A	ENSP00000436464.1	H0YES2

Frequencies

GnomAD3 genomes

AF:

0.00000696

AC:

AN:

143644

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:

0.000228

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000145

AC:

AN:

1033698

Hom.:

AF XY:

0.0000158

AC XY:

AN XY:

505504

show subpopulations

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

African (AFR)

AF:

0.0000443

AC:

AN:

22596

American (AMR)

AF:

0.00

AC:

AN:

17934

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15442

East Asian (EAS)

AF:

0.000198

AC:

AN:

30260

South Asian (SAS)

AF:

0.0000662

AC:

AN:

30200

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41466

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3316

European-Non Finnish (NFE)

AF:

0.00000602

AC:

AN:

830146

Other (OTH)

AF:

0.0000236

AC:

AN:

42338

⚠️ 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: 0.298

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:

0.00000696

AC:

AN:

143644

Hom.:

Cov.:

AF XY:

0.0000144

AC XY:

AN XY:

69500

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:

38842

American (AMR)

AF:

0.00

AC:

AN:

14172

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3350

East Asian (EAS)

AF:

0.00

AC:

AN:

4854

South Asian (SAS)

AF:

0.000228

AC:

AN:

4386

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9446

Middle Eastern (MID)

AF:

0.00

AC:

AN:

306

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

65430

Other (OTH)

AF:

0.00

AC:

AN:

1966

⚠️ 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:

0.00

Hom.:

278

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.5

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.

1-68486881-AACACACACACACACACACACACACACAC-AACACACACACACACACACACACACACACACACACACAC

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