Genetic Variant DDB2:c.1024-124G>C (chr11-47237713-G-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000107.3(DDB2):c.1024-124G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 961,424 control chromosomes in the GnomAD database, including 30,249 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.27 ( 6835 hom., cov: 30)

Exomes 𝑓: 0.21 ( 23414 hom. )

Consequence

DDB2
NM_000107.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.205

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 11-47237713-G-C is Benign according to our data. Variant chr11-47237713-G-C is described in ClinVar as [Benign]. Clinvar id is 1249280.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDB2	NM_000107.3 link	c.1024-124G>C		intron_variant	Intron 7 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.1024-124G>C		intron_variant	Intron 7 of 9	1	NM_000107.3	ENSP00000256996.4		Q92466-1

Frequencies

GnomAD3 genomes

AF:

0.267

AC:

40515

AN:

151694

Hom.:

6830

Cov.:

show subpopulations

Gnomad AFR

AF:

0.414

Gnomad AMI

AF:

0.0813

Gnomad AMR

AF:

0.275

Gnomad ASJ

AF:

0.131

Gnomad EAS

AF:

0.648

Gnomad SAS

AF:

0.232

Gnomad FIN

AF:

0.297

Gnomad MID

AF:

0.165

Gnomad NFE

AF:

0.157

Gnomad OTH

AF:

0.222

GnomAD4 exome

AF:

0.207

AC:

167401

AN:

809612

Hom.:

23414

Cov.:

AF XY:

0.205

AC XY:

86996

AN XY:

424500

show subpopulations

Gnomad4 AFR exome

AF:

0.411

Gnomad4 AMR exome

AF:

0.366

Gnomad4 ASJ exome

AF:

0.129

Gnomad4 EAS exome

AF:

0.655

Gnomad4 SAS exome

AF:

0.234

Gnomad4 FIN exome

AF:

0.264

Gnomad4 NFE exome

AF:

0.154

Gnomad4 OTH exome

AF:

0.203

GnomAD4 genome

AF:

0.267

AC:

40545

AN:

151812

Hom.:

6835

Cov.:

AF XY:

0.277

AC XY:

20522

AN XY:

74162

show subpopulations

Gnomad4 AFR

AF:

0.413

Gnomad4 AMR

AF:

0.275

Gnomad4 ASJ

AF:

0.131

Gnomad4 EAS

AF:

0.649

Gnomad4 SAS

AF:

0.233

Gnomad4 FIN

AF:

0.297

Gnomad4 NFE

AF:

0.157

Gnomad4 OTH

AF:

0.219

Alfa

AF:

0.108

Hom.:

149

Bravo

AF:

0.275

Asia WGS

AF:

0.346

AC:

1201

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 02, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

8.5

DANN

Benign

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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