ENST00000896514.1:c.-67A>G

Variant names:

• chr11-47214743-A-G
• rs3758666
• ENST00000896514.1:c.-67A>G

Variant summary

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

The ENST00000896514.1(DDB2):​c.-67A>G variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.695 in 321,550 control chromosomes in the GnomAD database, including 79,933 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.69 (36418 hom., cov: 26)
  • Exomes 𝑓: 0.70 (43515 hom.)
• Consequence: DDB2 ENST00000896514.1 splice_region
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.78
• Publications: 7 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=-0.99).
• BP6: Variant 11-47214743-A-G is Benign according to our data. Variant chr11-47214743-A-G is described in ClinVar as Benign. ClinVar VariationId is 1287348.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.748 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000896514.1. 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+69A>G		intron	N/A	NP_001386803.1	Q92466-1
	DDB2	NM_001399875.1		c.-65+69A>G		intron	N/A	NP_001386804.1	Q92466-1
	DDB2	NM_001399876.1		c.-67+69A>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.-67A>G		splice_region	Exon 1 of 11	ENSP00000566573.1
	DDB2	ENST00000896514.1		c.-67A>G		5_prime_UTR	Exon 1 of 11	ENSP00000566573.1
	DDB2	ENST00000967663.1		c.-67+243A>G		intron	N/A	ENSP00000637722.1

Frequencies

GnomAD3 genomes AF: 0.693 AC: 103658 AN: 149604 Hom.: 36411 Cov.: 26

Gnomad AFR AF: 0.643

Gnomad AMI AF: 0.719

Gnomad AMR AF: 0.667

Gnomad ASJ AF: 0.808

Gnomad EAS AF: 0.355

Gnomad SAS AF: 0.714

Gnomad FIN AF: 0.637

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.753

Gnomad OTH AF: 0.724

GnomAD4 exome AF: 0.697 AC: 119791 AN: 171846 Hom.: 43515 Cov.: 0 AF XY: 0.695 AC XY: 63363 AN XY: 91220

African (AFR) AF: 0.623 AC: 3089 AN: 4960

American (AMR) AF: 0.577 AC: 3592 AN: 6224

Ashkenazi Jewish (ASJ) AF: 0.794 AC: 3862 AN: 4864

East Asian (EAS) AF: 0.324 AC: 3870 AN: 11962

South Asian (SAS) AF: 0.685 AC: 19415 AN: 28358

European-Finnish (FIN) AF: 0.653 AC: 4659 AN: 7130

Middle Eastern (MID) AF: 0.752 AC: 495 AN: 658

European-Non Finnish (NFE) AF: 0.753 AC: 74221 AN: 98520

Other (OTH) AF: 0.718 AC: 6588 AN: 9170

GnomAD4 genome AF: 0.693 AC: 103701 AN: 149704 Hom.: 36418 Cov.: 26 AF XY: 0.686 AC XY: 50021 AN XY: 72952

African (AFR) AF: 0.643 AC: 26162 AN: 40688

American (AMR) AF: 0.667 AC: 10075 AN: 15114

Ashkenazi Jewish (ASJ) AF: 0.808 AC: 2791 AN: 3454

East Asian (EAS) AF: 0.354 AC: 1786 AN: 5046

South Asian (SAS) AF: 0.713 AC: 3393 AN: 4756

European-Finnish (FIN) AF: 0.637 AC: 6394 AN: 10042

Middle Eastern (MID) AF: 0.777 AC: 227 AN: 292

European-Non Finnish (NFE) AF: 0.753 AC: 50713 AN: 67336

Other (OTH) AF: 0.729 AC: 1516 AN: 2080

Alfa AF: 0.708 Hom.: 4554

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	-0.99
CADD	Benign	1.1
DANN	Benign	0.15
PhyloP100		-2.8
PromoterAI		0.012	Neutral

Splicing

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

Other links and lift over

dbSNP: rs3758666; hg19: chr11-47236294;