rs11039138

Positions:

• chr11-47227672-G-A
• chr11-47227672-G-C
• chr11-47227672-G-T

Variant summary

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

The NM_000107.3(DDB2):​c.457-5142G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 151,842 control chromosomes in the GnomAD database, including 6,454 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 0.26 (6454 hom., cov: 29)
• Consequence: DDB2 NM_000107.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.222

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDB2	NM_000107.3	c.457-5142G>A		intron_variant		ENST00000256996.9	NP_000098.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDB2	ENST00000256996.9	c.457-5142G>A		intron_variant		1	NM_000107.3	ENSP00000256996	P1

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39005 AN: 151724 Hom.: 6458 Cov.: 29

Gnomad AFR AF: 0.0715

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.0204

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.301

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.257 AC: 38994 AN: 151842 Hom.: 6454 Cov.: 29 AF XY: 0.251 AC XY: 18585 AN XY: 74180

Gnomad4 AFR AF: 0.0713

Gnomad4 AMR AF: 0.241

Gnomad4 ASJ AF: 0.388

Gnomad4 EAS AF: 0.0207

Gnomad4 SAS AF: 0.245

Gnomad4 FIN AF: 0.278

Gnomad4 NFE AF: 0.379

Gnomad4 OTH AF: 0.297

Alfa AF: 0.223 Hom.: 698

Bravo AF: 0.244

Asia WGS AF: 0.135 AC: 470 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.55

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: rs11039138; hg19: chr11-47249223;