rs1685404

Positions:

• chr11-47222114-G-C

Variant summary

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

The NM_000107.3(DDB2):​c.456+5065G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 152,020 control chromosomes in the GnomAD database, including 6,822 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 0.30 (6822 hom., cov: 32)
• Consequence: DDB2 NM_000107.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.63

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDB2	NM_000107.3	c.456+5065G>C		intron_variant		ENST00000256996.9	NP_000098.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDB2	ENST00000256996.9	c.456+5065G>C		intron_variant		1	NM_000107.3	ENSP00000256996	P1

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45318 AN: 151902 Hom.: 6811 Cov.: 32

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.451

Gnomad AMR AF: 0.358

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.317

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

GnomAD4 genome AF: 0.298 AC: 45362 AN: 152020 Hom.: 6822 Cov.: 32 AF XY: 0.297 AC XY: 22107 AN XY: 74316

Gnomad4 AFR AF: 0.242

Gnomad4 AMR AF: 0.358

Gnomad4 ASJ AF: 0.381

Gnomad4 EAS AF: 0.236

Gnomad4 SAS AF: 0.291

Gnomad4 FIN AF: 0.316

Gnomad4 NFE AF: 0.315

Gnomad4 OTH AF: 0.325

Alfa AF: 0.305 Hom.: 860

Bravo AF: 0.301

Asia WGS AF: 0.293 AC: 1024 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.14
DANN	Benign	0.24

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: rs1685404; hg19: chr11-47243665;