rs2957873

chr11-47227743-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.457-5071G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.691 in 151,894 control chromosomes in the GnomAD database, including 37,677 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 0.69 (37677 hom., cov: 31)
• Consequence: DDB2 NM_000107.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.928

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=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDB2	NM_000107.3	c.457-5071G>A		intron_variant		ENST00000256996.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDB2	ENST00000256996.9	c.457-5071G>A		intron_variant		1	NM_000107.3	P1

Frequencies

GnomAD3 genomes AF: 0.691 AC: 104883 AN: 151776 Hom.: 37649 Cov.: 31

Gnomad AFR AF: 0.544

Gnomad AMI AF: 0.896

Gnomad AMR AF: 0.690

Gnomad ASJ AF: 0.855

Gnomad EAS AF: 0.312

Gnomad SAS AF: 0.649

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.804

Gnomad OTH AF: 0.744

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

GnomAD4 genome AF: 0.691 AC: 104969 AN: 151894 Hom.: 37677 Cov.: 31 AF XY: 0.680 AC XY: 50461 AN XY: 74226

Gnomad4 AFR AF: 0.545

Gnomad4 AMR AF: 0.689

Gnomad4 ASJ AF: 0.855

Gnomad4 EAS AF: 0.311

Gnomad4 SAS AF: 0.649

Gnomad4 FIN AF: 0.657

Gnomad4 NFE AF: 0.804

Gnomad4 OTH AF: 0.748

Alfa AF: 0.791 Hom.: 81095

Bravo AF: 0.686

Asia WGS AF: 0.545 AC: 1897 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	2.9
Dann	Benign	0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2957873; hg19: chr11-47249294;