rs3781619

Variant names:

• chr11-47233766-G-A
• rs3781619
• NM_000107.3:c.602+807G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 26 publications found

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 Gene-Disease associations (from GenCC):

• xeroderma pigmentosum group E

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), ClinGen, Genomics England PanelApp
• xeroderma pigmentosum

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DDB2	NM_000107.3	c.602+807G>A		intron_variant	Intron 4 of 9	ENST00000256996.9	NP_000098.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDB2	ENST00000256996.9	c.602+807G>A		intron_variant	Intron 4 of 9	1	NM_000107.3	ENSP00000256996.4

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

African (AFR) AF: 0.391 AC: 16156 AN: 41322

American (AMR) AF: 0.275 AC: 4184 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 455 AN: 3468

East Asian (EAS) AF: 0.650 AC: 3347 AN: 5146

South Asian (SAS) AF: 0.234 AC: 1129 AN: 4818

European-Finnish (FIN) AF: 0.294 AC: 3071 AN: 10434

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.156 AC: 10631 AN: 67936

Other (OTH) AF: 0.212 AC: 447 AN: 2104

Alfa AF: 0.218 Hom.: 3718

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
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3781619; hg19: chr11-47255317;