11-47214743-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001399874.1(DDB2):c.-67+69A>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 321,550 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 NM_001399874.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.78

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDB2	NM_001399874.1	c.-67+69A>G		intron_variant
DDB2	NM_001399875.1	c.-65+69A>G		intron_variant
DDB2	NM_001399876.1	c.-67+69A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDB2	ENST00000614825.4	c.-65+69A>G		intron_variant		3
DDB2	ENST00000622878.4	c.-67+69A>G		intron_variant		4

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

Gnomad4 AFR exome AF: 0.623

Gnomad4 AMR exome AF: 0.577

Gnomad4 ASJ exome AF: 0.794

Gnomad4 EAS exome AF: 0.324

Gnomad4 SAS exome AF: 0.685

Gnomad4 FIN exome AF: 0.653

Gnomad4 NFE exome AF: 0.753

Gnomad4 OTH exome AF: 0.718

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

Gnomad4 AFR AF: 0.643

Gnomad4 AMR AF: 0.667

Gnomad4 ASJ AF: 0.808

Gnomad4 EAS AF: 0.354

Gnomad4 SAS AF: 0.713

Gnomad4 FIN AF: 0.637

Gnomad4 NFE AF: 0.753

Gnomad4 OTH AF: 0.729

Alfa AF: 0.708 Hom.: 4554

Bravo AF: 0.688

Asia WGS AF: 0.614 AC: 2137 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	1.1
Dann	Benign	0.15

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3758666; hg19: chr11-47236294;