rs1685404

Variant names:

• chr11-47222114-G-C
• rs1685404
• NM_000107.3:c.456+5065G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000107.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDB2	NM_000107.3	MANE Select	c.456+5065G>C		intron	N/A	NP_000098.1
	DDB2	NM_001399874.1		c.456+5065G>C		intron	N/A	NP_001386803.1
	DDB2	NM_001399875.1		c.456+5065G>C		intron	N/A	NP_001386804.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDB2	ENST00000256996.9	TSL:1 MANE Select	c.456+5065G>C		intron	N/A	ENSP00000256996.4
	DDB2	ENST00000378603.7	TSL:1	c.264+5642G>C		intron	N/A	ENSP00000367866.3
	DDB2	ENST00000378600.7	TSL:1	c.456+5065G>C		intron	N/A	ENSP00000367863.3

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

African (AFR) AF: 0.242 AC: 10030 AN: 41472

American (AMR) AF: 0.358 AC: 5462 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.381 AC: 1323 AN: 3470

East Asian (EAS) AF: 0.236 AC: 1222 AN: 5172

South Asian (SAS) AF: 0.291 AC: 1401 AN: 4822

European-Finnish (FIN) AF: 0.316 AC: 3334 AN: 10550

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

European-Non Finnish (NFE) AF: 0.315 AC: 21396 AN: 67968

Other (OTH) AF: 0.325 AC: 686 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.14
DANN	Benign	0.24
PhyloP100		-1.6
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: rs1685404; hg19: chr11-47243665;