NM_000107.3:c.1189-21T>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000107.3(DDB2):c.1189-21T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.654 in 1,610,336 control chromosomes in the GnomAD database, including 354,776 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.58 ( 27322 hom., cov: 31)

Exomes 𝑓: 0.66 ( 327454 hom. )

Consequence

DDB2
NM_000107.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.151

Publications

52 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 11-47238117-T-C is Benign according to our data. Variant chr11-47238117-T-C is described in ClinVar as Benign. ClinVar VariationId is 1237094.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000107.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
DDB2	NM_000107.3	MANE Select	c.1189-21T>C	intron	N/A	NP_000098.1
DDB2	NM_001399874.1		c.1189-21T>C	intron	N/A	NP_001386803.1
DDB2	NM_001399875.1		c.1189-21T>C	intron	N/A	NP_001386804.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
DDB2	ENST00000256996.9	TSL:1 MANE Select	c.1189-21T>C	intron	N/A	ENSP00000256996.4
DDB2	ENST00000378603.7	TSL:1	c.997-21T>C	intron	N/A	ENSP00000367866.3
DDB2	ENST00000378600.7	TSL:1	c.622-21T>C	intron	N/A	ENSP00000367863.3

Frequencies

GnomAD3 genomes

AF:

0.580

AC:

88090

AN:

151896

Hom.:

27301

Cov.:

show subpopulations

Gnomad AFR

AF:

0.385

Gnomad AMI

AF:

0.867

Gnomad AMR

AF:

0.628

Gnomad ASJ

AF:

0.773

Gnomad EAS

AF:

0.255

Gnomad SAS

AF:

0.534

Gnomad FIN

AF:

0.573

Gnomad MID

AF:

0.709

Gnomad NFE

AF:

0.700

Gnomad OTH

AF:

0.644

GnomAD2 exomes

AF:

0.599

AC:

148264

AN:

247400

AF XY:

0.609

show subpopulations

Gnomad AFR exome

AF:

0.376

Gnomad AMR exome

AF:

0.554

Gnomad ASJ exome

AF:

0.778

Gnomad EAS exome

AF:

0.241

Gnomad FIN exome

AF:

0.580

Gnomad NFE exome

AF:

0.704

Gnomad OTH exome

AF:

0.675

GnomAD4 exome

AF:

0.662

AC:

965777

AN:

1458322

Hom.:

327454

Cov.:

AF XY:

0.661

AC XY:

479460

AN XY:

725356

show subpopulations

African (AFR)

AF:

0.381

AC:

12757

AN:

33446

American (AMR)

AF:

0.566

AC:

25035

AN:

44240

Ashkenazi Jewish (ASJ)

AF:

0.780

AC:

20342

AN:

26096

East Asian (EAS)

AF:

0.258

AC:

10213

AN:

39654

South Asian (SAS)

AF:

0.538

AC:

46249

AN:

85898

European-Finnish (FIN)

AF:

0.590

AC:

31453

AN:

53290

Middle Eastern (MID)

AF:

0.709

AC:

4087

AN:

5764

European-Non Finnish (NFE)

AF:

0.700

AC:

776429

AN:

1109662

Other (OTH)

AF:

0.651

AC:

39212

AN:

60272

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

17588

35176

52764

70352

87940

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19308

38616

57924

77232

96540

<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:

0.580

AC:

88160

AN:

152014

Hom.:

27322

Cov.:

AF XY:

0.571

AC XY:

42437

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.385

AC:

15974

AN:

41446

American (AMR)

AF:

0.628

AC:

9592

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.773

AC:

2681

AN:

3468

East Asian (EAS)

AF:

0.254

AC:

1312

AN:

5166

South Asian (SAS)

AF:

0.535

AC:

2577

AN:

4820

European-Finnish (FIN)

AF:

0.573

AC:

6058

AN:

10580

Middle Eastern (MID)

AF:

0.707

AC:

208

AN:

294

European-Non Finnish (NFE)

AF:

0.700

AC:

47599

AN:

67952

Other (OTH)

AF:

0.648

AC:

1368

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1779

3559

5338

7118

8897

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

728

1456

2184

2912

3640

<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:

0.594

Hom.:

10651

Bravo

AF:

0.576

Asia WGS

AF:

0.445

AC:

1549

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Jan 10, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Xeroderma pigmentosum, group E

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

7.5

(source)

DANN

Benign

0.68

PhyloP100

0.15

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

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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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over