chr11-47227672-G-A

Variant names:

• chr11-47227672-G-A
• rs11039138
• NM_000107.3:c.457-5142G>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.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
• Publications: 6 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=-0.88).
• 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 rank	MANE	Protein	UniProt
DDB2	NM_000107.3	c.457-5142G>A		intron_variant	Intron 3 of 9	ENST00000256996.9	NP_000098.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDB2	ENST00000256996.9	c.457-5142G>A		intron_variant	Intron 3 of 9	1	NM_000107.3	ENSP00000256996.4

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

African (AFR) AF: 0.0713 AC: 2956 AN: 41440

American (AMR) AF: 0.241 AC: 3665 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 1345 AN: 3468

East Asian (EAS) AF: 0.0207 AC: 107 AN: 5174

South Asian (SAS) AF: 0.245 AC: 1180 AN: 4820

European-Finnish (FIN) AF: 0.278 AC: 2922 AN: 10512

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.379 AC: 25764 AN: 67894

Other (OTH) AF: 0.297 AC: 626 AN: 2108

Alfa AF: 0.319 Hom.: 11396

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
PhyloP100		0.22
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: rs11039138; hg19: chr11-47249223;