rs4647709

Positions:

• chr11-47215808-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.742

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
DDB2	NM_000107.3	c.128-528C>T		intron_variant		ENST00000256996.9	NP_000098.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDB2	ENST00000256996.9	c.128-528C>T		intron_variant		1	NM_000107.3	ENSP00000256996.4

Frequencies

GnomAD3 genomes AF: 0.0627 AC: 9539 AN: 152064 Hom.: 394 Cov.: 31

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.: 0 AF XY: 0.0682 AC XY: 4049 AN XY: 59406

Gnomad4 AFR exome AF: 0.0108

Gnomad4 AMR exome AF: 0.0392

Gnomad4 ASJ exome AF: 0.0764

Gnomad4 EAS exome AF: 0.000441

Gnomad4 SAS exome AF: 0.0526

Gnomad4 FIN exome AF: 0.0737

Gnomad4 NFE exome AF: 0.0829

Gnomad4 OTH exome AF: 0.0732

GnomAD4 genome AF: 0.0626 AC: 9531 AN: 152182 Hom.: 392 Cov.: 31 AF XY: 0.0619 AC XY: 4609 AN XY: 74402

Gnomad4 AFR AF: 0.0164

Gnomad4 AMR AF: 0.0504

Gnomad4 ASJ AF: 0.0769

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0539

Gnomad4 FIN AF: 0.0821

Gnomad4 NFE AF: 0.0932

Gnomad4 OTH AF: 0.0639

Alfa AF: 0.0834 Hom.: 275

Bravo AF: 0.0581

Asia WGS AF: 0.0210 AC: 74 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	12
DANN	Benign	0.70

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

LitVar

Other links and lift over

dbSNP: rs4647709; hg19: chr11-47237359;