rs7395581

Variant names:

• chr11-47224846-G-A
• rs7395581
• NM_000107.3:c.456+7797G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-47224846-G-A
• chr11-47224846-G-C
• chr11-47224846-G-T

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+7797G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.616 in 151,588 control chromosomes in the GnomAD database, including 29,716 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 0.62 (29716 hom., cov: 29)
• Consequence: DDB2 NM_000107.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.208
• Publications: 27 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), Genomics England PanelApp, ClinGen
• 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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.696 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDB2	NM_000107.3	MANE Select	c.456+7797G>A		intron	N/A	NP_000098.1	Q92466-1
	DDB2	NM_001399874.1		c.456+7797G>A		intron	N/A	NP_001386803.1	Q92466-1
	DDB2	NM_001399875.1		c.456+7797G>A		intron	N/A	NP_001386804.1	Q92466-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDB2	ENST00000256996.9	TSL:1 MANE Select	c.456+7797G>A		intron	N/A	ENSP00000256996.4	Q92466-1
	DDB2	ENST00000378603.7	TSL:1	c.265-7968G>A		intron	N/A	ENSP00000367866.3	Q92466-4
	DDB2	ENST00000378600.7	TSL:1	c.456+7797G>A		intron	N/A	ENSP00000367863.3	Q92466-2

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93265 AN: 151472 Hom.: 29684 Cov.: 29

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.867

Gnomad AMR AF: 0.626

Gnomad ASJ AF: 0.778

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.577

Gnomad MID AF: 0.736

Gnomad NFE AF: 0.701

Gnomad OTH AF: 0.671

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

GnomAD4 genome AF: 0.616 AC: 93356 AN: 151588 Hom.: 29716 Cov.: 29 AF XY: 0.606 AC XY: 44868 AN XY: 74066

African (AFR) AF: 0.511 AC: 21104 AN: 41314

American (AMR) AF: 0.626 AC: 9528 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.778 AC: 2695 AN: 3466

East Asian (EAS) AF: 0.261 AC: 1328 AN: 5096

South Asian (SAS) AF: 0.540 AC: 2593 AN: 4804

European-Finnish (FIN) AF: 0.577 AC: 6042 AN: 10464

Middle Eastern (MID) AF: 0.736 AC: 215 AN: 292

European-Non Finnish (NFE) AF: 0.701 AC: 47641 AN: 67920

Other (OTH) AF: 0.674 AC: 1419 AN: 2104

Alfa AF: 0.683 Hom.: 47153

Bravo AF: 0.615

Asia WGS AF: 0.467 AC: 1627 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.8
DANN	Benign	0.77
PhyloP100		0.21
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: rs7395581; hg19: chr11-47246397;