rs1050244

Variant summary

Our verdict is Benign. Variant got -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:2

Conservation

PhyloP100: 1.21

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	UniProt
DDB2	NM_000107.3 linkuse as main transcript	c.*77C>T		3_prime_UTR_variant	10/10	ENST00000256996.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDB2	ENST00000256996.9 linkuse as main transcript	c.*77C>T		3_prime_UTR_variant	10/10	1	NM_000107.3	P1	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

Gnomad4 AFR exome

AF:

0.0230

Gnomad4 AMR exome

AF:

0.0140

Gnomad4 ASJ exome

AF:

0.0126

Gnomad4 EAS exome

AF:

0.0352

Gnomad4 SAS exome

AF:

0.113

Gnomad4 FIN exome

AF:

0.0499

Gnomad4 NFE exome

AF:

0.0367

Gnomad4 OTH exome

AF:

0.0419

GnomAD4 genome

AF:

0.0341

AC:

5176

AN:

151748

Hom.:

122

Cov.:

AF XY:

0.0358

AC XY:

2656

AN XY:

74114

show subpopulations

Gnomad4 AFR

AF:

0.0227

Gnomad4 AMR

AF:

0.0166

Gnomad4 ASJ

AF:

0.0156

Gnomad4 EAS

AF:

0.0421

Gnomad4 SAS

AF:

0.118

Gnomad4 FIN

AF:

0.0468

Gnomad4 NFE

AF:

0.0377

Gnomad4 OTH

AF:

0.0319

Alfa

AF:

0.0343

Hom.:

Bravo

AF:

0.0289

Asia WGS

AF:

0.117

AC:

407

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Xeroderma pigmentosum, group E

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 28, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

Cadd

Benign

Dann

Benign

0.56

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over