dbSNP rs4647709: DDB2:c.128-528C>T (chr11-47215808-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000107.3(DDB2):c.128-528C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0655 in 263,176 control chromosomes in the GnomAD database, including 740 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.063 ( 392 hom., cov: 31)

Exomes 𝑓: 0.069 ( 348 hom. )

Consequence

DDB2
NM_000107.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.742

Publications

21 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), ClinGen, Genomics England PanelApp
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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0913 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDB2	NM_000107.3 link	c.128-528C>T		intron_variant	Intron 1 of 9	ENST00000256996.9	NP_000098.1	Q92466-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDB2	ENST00000256996.9 link	c.128-528C>T		intron_variant	Intron 1 of 9	1	NM_000107.3	ENSP00000256996.4		Q92466-1

Frequencies

GnomAD3 genomes

AF:

0.0627

AC:

9539

AN:

152064

Hom.:

394

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0164

Gnomad AMI

AF:

0.198

Gnomad AMR

AF:

0.0504

Gnomad ASJ

AF:

0.0769

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.0547

Gnomad FIN

AF:

0.0821

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0932

Gnomad OTH

AF:

0.0656

GnomAD4 exome

AF:

0.0694

AC:

7701

AN:

110994

Hom.:

348

Cov.:

AF XY:

0.0682

AC XY:

4049

AN XY:

59406

show subpopulations

African (AFR)

AF:

0.0108

AC:

AN:

2860

American (AMR)

AF:

0.0392

AC:

161

AN:

4108

Ashkenazi Jewish (ASJ)

AF:

0.0764

AC:

198

AN:

2592

East Asian (EAS)

AF:

0.000441

AC:

AN:

4534

South Asian (SAS)

AF:

0.0526

AC:

1059

AN:

20150

European-Finnish (FIN)

AF:

0.0737

AC:

392

AN:

5318

Middle Eastern (MID)

AF:

0.0644

AC:

AN:

404

European-Non Finnish (NFE)

AF:

0.0829

AC:

5424

AN:

65458

Other (OTH)

AF:

0.0732

AC:

408

AN:

5570

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

336

672

1007

1343

1679

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

136

170

<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:

0.0626

AC:

9531

AN:

152182

Hom.:

392

Cov.:

AF XY:

0.0619

AC XY:

4609

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.0164

AC:

681

AN:

41540

American (AMR)

AF:

0.0504

AC:

769

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.0769

AC:

267

AN:

3472

East Asian (EAS)

AF:

0.00116

AC:

AN:

5176

South Asian (SAS)

AF:

0.0539

AC:

260

AN:

4820

European-Finnish (FIN)

AF:

0.0821

AC:

869

AN:

10590

Middle Eastern (MID)

AF:

0.0918

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0932

AC:

6336

AN:

67998

Other (OTH)

AF:

0.0639

AC:

135

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

458

915

1373

1830

2288

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

232

348

464

580

<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:

0.0826

Hom.:

310

Bravo

AF:

0.0581

Asia WGS

AF:

0.0210

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

(source)

DANN

Benign

0.70

PhyloP100

0.74

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over