1-68486881-AACACACACACACACACACACACACACAC-AACACACACACACACACACAC

Variant names:

• chr1-68486881-AACACACAC-A
• rs55915411
• NM_001114120.3:c.769+48_769+55delGTGTGTGT

Variant summary

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

The NM_001114120.3(DEPDC1):​c.769+48_769+55delGTGTGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00599 in 1,173,200 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0021 (1 hom., cov: 0)
  • Exomes 𝑓: 0.0065 (0 hom.)
• Consequence: DEPDC1 NM_001114120.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.95
• Publications: 0 publications found

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]

ACMG classification

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

• PM2: Variant has high frequency in the AMR (0.012) population. However there is too low homozygotes in high coverage region: (expected more than 10, got 1).

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+48_769+55delGTGTGTGT		intron	N/A	NP_001107592.1	Q5TB30-5
	DEPDC1	NM_017779.6		c.769+48_769+55delGTGTGTGT		intron	N/A	NP_060249.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEPDC1	ENST00000456315.7	TSL:1 MANE Select	c.769+48_769+55delGTGTGTGT		intron	N/A	ENSP00000412292.2	Q5TB30-5
	DEPDC1	ENST00000370966.9	TSL:1	c.769+48_769+55delGTGTGTGT		intron	N/A	ENSP00000360005.5	Q5TB30-2
	DEPDC1	ENST00000489862.1	TSL:1	n.472+48_472+55delGTGTGTGT		intron	N/A	ENSP00000436464.1	H0YES2

Frequencies

GnomAD3 genomes AF: 0.00204 AC: 293 AN: 143620 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.00592

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000917

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000824

Gnomad SAS AF: 0.00160

Gnomad FIN AF: 0.000424

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000459

Gnomad OTH AF: 0.00254

GnomAD4 exome AF: 0.00653 AC: 6727 AN: 1029492 Hom.: 0 AF XY: 0.00652 AC XY: 3283 AN XY: 503458

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

African (AFR) AF: 0.00897 AC: 202 AN: 22508

American (AMR) AF: 0.0134 AC: 239 AN: 17826

Ashkenazi Jewish (ASJ) AF: 0.00182 AC: 28 AN: 15416

East Asian (EAS) AF: 0.00288 AC: 87 AN: 30208

South Asian (SAS) AF: 0.00637 AC: 192 AN: 30142

European-Finnish (FIN) AF: 0.00356 AC: 147 AN: 41300

Middle Eastern (MID) AF: 0.00121 AC: 4 AN: 3306

European-Non Finnish (NFE) AF: 0.00673 AC: 5564 AN: 826574

Other (OTH) AF: 0.00625 AC: 264 AN: 42212

⚠️ 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.

GnomAD4 genome AF: 0.00206 AC: 296 AN: 143708 Hom.: 1 Cov.: 0 AF XY: 0.00221 AC XY: 154 AN XY: 69594

African (AFR) AF: 0.00598 AC: 233 AN: 38942

American (AMR) AF: 0.000916 AC: 13 AN: 14186

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3350

East Asian (EAS) AF: 0.000826 AC: 4 AN: 4842

South Asian (SAS) AF: 0.00160 AC: 7 AN: 4380

European-Finnish (FIN) AF: 0.000424 AC: 4 AN: 9436

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 286

European-Non Finnish (NFE) AF: 0.000459 AC: 30 AN: 65414

Other (OTH) AF: 0.00253 AC: 5 AN: 1980

Alfa AF: 0.00 Hom.: 278

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.9
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs55915411; hg19: chr1-68952564;