11-47214747-A-G

Variant names:

• chr11-47214747-A-G
• rs3758667
• NM_001399874.1:c.-67+73A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001399874.1(DDB2):​c.-67+73A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.695 in 321,560 control chromosomes in the GnomAD database, including 79,844 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.69 (36364 hom., cov: 25)
  • Exomes 𝑓: 0.70 (43480 hom.)
• Consequence: DDB2 NM_001399874.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0440
• Publications: 8 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 11-47214747-A-G is Benign according to our data. Variant chr11-47214747-A-G is described in ClinVar as Benign. ClinVar VariationId is 1250132.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.747 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001399874.1. 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_001399874.1		c.-67+73A>G		intron	N/A	NP_001386803.1	Q92466-1
	DDB2	NM_001399875.1		c.-65+73A>G		intron	N/A	NP_001386804.1	Q92466-1
	DDB2	NM_001399876.1		c.-67+73A>G		intron	N/A	NP_001386805.1	Q92466-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDB2	ENST00000896514.1		c.-67+4A>G		splice_region intron	N/A	ENSP00000566573.1
	DDB2	ENST00000967663.1		c.-67+247A>G		intron	N/A	ENSP00000637722.1
	DDB2	ENST00000967664.1		c.-67+108A>G		intron	N/A	ENSP00000637723.1

Frequencies

GnomAD3 genomes AF: 0.693 AC: 103525 AN: 149466 Hom.: 36356 Cov.: 25

Gnomad AFR AF: 0.643

Gnomad AMI AF: 0.717

Gnomad AMR AF: 0.667

Gnomad ASJ AF: 0.808

Gnomad EAS AF: 0.355

Gnomad SAS AF: 0.713

Gnomad FIN AF: 0.636

Gnomad MID AF: 0.777

Gnomad NFE AF: 0.753

Gnomad OTH AF: 0.726

GnomAD4 exome AF: 0.696 AC: 119756 AN: 171990 Hom.: 43480 Cov.: 0 AF XY: 0.694 AC XY: 63220 AN XY: 91138

African (AFR) AF: 0.624 AC: 3143 AN: 5034

American (AMR) AF: 0.577 AC: 3594 AN: 6226

Ashkenazi Jewish (ASJ) AF: 0.794 AC: 3887 AN: 4896

East Asian (EAS) AF: 0.322 AC: 3886 AN: 12070

South Asian (SAS) AF: 0.685 AC: 19540 AN: 28534

European-Finnish (FIN) AF: 0.653 AC: 4680 AN: 7162

Middle Eastern (MID) AF: 0.752 AC: 492 AN: 654

European-Non Finnish (NFE) AF: 0.753 AC: 73954 AN: 98252

Other (OTH) AF: 0.718 AC: 6580 AN: 9162

GnomAD4 genome AF: 0.692 AC: 103570 AN: 149570 Hom.: 36364 Cov.: 25 AF XY: 0.685 AC XY: 49938 AN XY: 72858

African (AFR) AF: 0.643 AC: 26107 AN: 40612

American (AMR) AF: 0.666 AC: 10062 AN: 15100

Ashkenazi Jewish (ASJ) AF: 0.808 AC: 2793 AN: 3456

East Asian (EAS) AF: 0.353 AC: 1787 AN: 5058

South Asian (SAS) AF: 0.713 AC: 3377 AN: 4738

European-Finnish (FIN) AF: 0.636 AC: 6377 AN: 10034

Middle Eastern (MID) AF: 0.778 AC: 224 AN: 288

European-Non Finnish (NFE) AF: 0.753 AC: 50684 AN: 67312

Other (OTH) AF: 0.731 AC: 1518 AN: 2078

Alfa AF: 0.710 Hom.: 4289

Bravo AF: 0.688

Asia WGS AF: 0.614 AC: 2137 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.2
DANN	Benign	0.56
PhyloP100		0.044
PromoterAI		-0.030	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3758667; hg19: chr11-47236298;