NM_000107.3:c.*77C>T

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.*77C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0398 in 1,531,978 control chromosomes in the GnomAD database, including 1,636 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.034 ( 122 hom., cov: 31)

Exomes 𝑓: 0.040 ( 1514 hom. )

Consequence

DDB2
NM_000107.3 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.21

Publications

13 publications found

Variant links:

COSMIC-nc: COSV104563737

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=-0.8).

BP6

Variant 11-47238926-C-T is Benign according to our data. Variant chr11-47238926-C-T is described in ClinVar as Benign. ClinVar VariationId is 304930.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDB2	NM_000107.3 link	c.*77C>T		3_prime_UTR_variant	Exon 10 of 10	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.*77C>T		3_prime_UTR_variant	Exon 10 of 10	1	NM_000107.3	ENSP00000256996.4		Q92466-1

Frequencies

GnomAD3 genomes

AF:

0.0342

AC:

5179

AN:

151630

Hom.:

124

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0226

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.0167

Gnomad ASJ

AF:

0.0156

Gnomad EAS

AF:

0.0428

Gnomad SAS

AF:

0.119

Gnomad FIN

AF:

0.0468

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0377

Gnomad OTH

AF:

0.0318

GnomAD4 exome

AF:

0.0405

AC:

55857

AN:

1380230

Hom.:

1514

Cov.:

AF XY:

0.0429

AC XY:

29580

AN XY:

689484

show subpopulations

African (AFR)

AF:

0.0230

AC:

735

AN:

31942

American (AMR)

AF:

0.0140

AC:

594

AN:

42516

Ashkenazi Jewish (ASJ)

AF:

0.0126

AC:

320

AN:

25348

East Asian (EAS)

AF:

0.0352

AC:

1364

AN:

38792

South Asian (SAS)

AF:

0.113

AC:

9462

AN:

83758

European-Finnish (FIN)

AF:

0.0499

AC:

2483

AN:

49764

Middle Eastern (MID)

AF:

0.0259

AC:

113

AN:

4364

European-Non Finnish (NFE)

AF:

0.0367

AC:

38376

AN:

1046200

Other (OTH)

AF:

0.0419

AC:

2410

AN:

57546

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

2704

5409

8113

10818

13522

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1396

2792

4188

5584

6980

<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:

0.0341

AC:

5176

AN:

151748

Hom.:

122

Cov.:

AF XY:

0.0358

AC XY:

2656

AN XY:

74114

show subpopulations

African (AFR)

AF:

0.0227

AC:

940

AN:

41392

American (AMR)

AF:

0.0166

AC:

253

AN:

15216

Ashkenazi Jewish (ASJ)

AF:

0.0156

AC:

AN:

3466

East Asian (EAS)

AF:

0.0421

AC:

216

AN:

5130

South Asian (SAS)

AF:

0.118

AC:

567

AN:

4802

European-Finnish (FIN)

AF:

0.0468

AC:

492

AN:

10504

Middle Eastern (MID)

AF:

0.0137

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0377

AC:

2562

AN:

67936

Other (OTH)

AF:

0.0319

AC:

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

Heterozygous variant carriers

252

504

756

1008

1260

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

210

280

350

<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:

0.0339

Hom.:

Bravo

AF:

0.0289

Asia WGS

AF:

0.117

AC:

407

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

Feb 28, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Xeroderma pigmentosum, group E

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

(source)

DANN

Benign

0.56

PhyloP100

1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over