Genetic Variant DDB2:c.-123_-122delGA (chr11-47214602-AAG-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001399874.1(DDB2):c.-123_-122delGA variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.045 in 159,796 control chromosomes in the GnomAD database, including 211 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.046 ( 204 hom., cov: 30)

Exomes 𝑓: 0.035 ( 7 hom. )

Consequence

DDB2
NM_001399874.1 5_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0470

Publications

1 publications found

Variant links:

Genes affected

DDB2 (HGNC:2718): (damage specific DNA binding protein 2) This gene encodes a protein that is necessary for the repair of ultraviolet light-damaged DNA. This protein is the smaller subunit of a heterodimeric protein complex that participates in nucleotide excision repair, and this complex mediates the ubiquitylation of histones H3 and H4, which facilitates the cellular response to DNA damage. This subunit appears to be required for DNA binding. Mutations in this gene cause xeroderma pigmentosum complementation group E, a recessive disease that is characterized by an increased sensitivity to UV light and a high predisposition for skin cancer development, in some cases accompanied by neurological abnormalities. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

DDB2 Gene-Disease associations (from GenCC):

xeroderma pigmentosum group E
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, ClinGen
xeroderma pigmentosum
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

DDB2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 11-47214602-AAG-A is Benign according to our data. Variant chr11-47214602-AAG-A is described in ClinVar as Benign. ClinVar VariationId is 1240976.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.066 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001399874.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
DDB2	NM_001399874.1	c.-123_-122delGA	5_prime_UTR	Exon 1 of 11	NP_001386803.1	Q92466-1
DDB2	NM_001399875.1	c.-121_-120delGA	5_prime_UTR	Exon 1 of 11	NP_001386804.1	Q92466-1
DDB2	NM_001399876.1	c.-123_-122delGA	5_prime_UTR	Exon 1 of 7	NP_001386805.1	Q92466-2

Ensembl Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein
DDB2	ENST00000896514.1	c.-192_-191delGA	5_prime_UTR	Exon 1 of 11	ENSP00000566573.1
DDB2	ENST00000967664.1	c.-88_-87delGA	5_prime_UTR	Exon 1 of 11	ENSP00000637723.1
DDB2	ENST00000967665.1	c.-123_-122delGA	5_prime_UTR	Exon 1 of 11	ENSP00000637724.1

Frequencies

GnomAD3 genomes

AF:

0.0456

AC:

6888

AN:

151062

Hom.:

204

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0117

Gnomad AMI

AF:

0.198

Gnomad AMR

AF:

0.0338

Gnomad ASJ

AF:

0.0528

Gnomad EAS

AF:

0.000780

Gnomad SAS

AF:

0.0220

Gnomad FIN

AF:

0.0706

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0677

Gnomad OTH

AF:

0.0419

GnomAD4 exome

AF:

0.0346

AC:

298

AN:

8624

Hom.:

AF XY:

0.0326

AC XY:

156

AN XY:

4792

show subpopulations

African (AFR)

AF:

0.0119

AC:

AN:

American (AMR)

AF:

0.0141

AC:

AN:

1206

Ashkenazi Jewish (ASJ)

AF:

0.0407

AC:

AN:

172

East Asian (EAS)

AF:

0.0133

AC:

AN:

602

South Asian (SAS)

AF:

0.0215

AC:

AN:

1486

European-Finnish (FIN)

AF:

0.0208

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0488

AC:

223

AN:

4574

Other (OTH)

AF:

0.0209

AC:

AN:

430

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.0456

AC:

6886

AN:

151172

Hom.:

204

Cov.:

AF XY:

0.0449

AC XY:

3318

AN XY:

73840

show subpopulations

African (AFR)

AF:

0.0117

AC:

482

AN:

41224

American (AMR)

AF:

0.0338

AC:

512

AN:

15154

Ashkenazi Jewish (ASJ)

AF:

0.0528

AC:

183

AN:

3464

East Asian (EAS)

AF:

0.000782

AC:

AN:

5118

South Asian (SAS)

AF:

0.0218

AC:

104

AN:

4766

European-Finnish (FIN)

AF:

0.0706

AC:

736

AN:

10418

Middle Eastern (MID)

AF:

0.0578

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0677

AC:

4584

AN:

67742

Other (OTH)

AF:

0.0415

AC:

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

318

636

953

1271

1589

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

160

240

320

400

<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:

0.0201

Hom.:

Bravo

AF:

0.0419

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.047

Splicing

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

Publications

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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