rs3781619

chr11-47233766-G-A

Variant summary

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

The NM_000107.3(DDB2):c.602+807G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 151,674 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: 31)
• Consequence: DDB2 NM_000107.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDB2	NM_000107.3	c.602+807G>A		intron_variant		ENST00000256996.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDB2	ENST00000256996.9	c.602+807G>A		intron_variant		1	NM_000107.3	P1

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39517 AN: 151556 Hom.: 6452 Cov.: 31

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.0813

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.649

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.216

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

GnomAD4 genome AF: 0.261 AC: 39537 AN: 151674 Hom.: 6454 Cov.: 31 AF XY: 0.270 AC XY: 20033 AN XY: 74070

Gnomad4 AFR AF: 0.391

Gnomad4 AMR AF: 0.275

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.650

Gnomad4 SAS AF: 0.234

Gnomad4 FIN AF: 0.294

Gnomad4 NFE AF: 0.156

Gnomad4 OTH AF: 0.212

Alfa AF: 0.188 Hom.: 1561

Bravo AF: 0.268

Asia WGS AF: 0.344 AC: 1192 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.37
Dann	Benign	0.48

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: rs3781619; hg19: chr11-47255317;