11-47214602-AAG-A

Position:

• chr11-47214602-AAG-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001399874.1(DDB2):​c.-123_-122del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.045 in 159,796 control chromosomes in the GnomAD database, including 211 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.046 (204 hom., cov: 30)
  • Exomes 𝑓: 0.035 (7 hom.)
• Consequence: DDB2 NM_001399874.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0470

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 -10 ACMG points.

• BP6: Variant 11-47214602-AAG-A is Benign according to our data. Variant chr11-47214602-AAG-A is described in ClinVar as [Benign]. Clinvar id is 1240976.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.066 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDB2	NM_001399874.1	c.-123_-122del		5_prime_UTR_variant	1/11		NP_001386803.1
DDB2	NM_001399875.1	c.-121_-120del		5_prime_UTR_variant	1/11		NP_001386804.1
DDB2	NM_001399876.1	c.-123_-122del		5_prime_UTR_variant	1/7		NP_001386805.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDB2	ENST00000614825.4	c.-121_-120del		5_prime_UTR_variant	1/6	3		ENSP00000483718
DDB2	ENST00000622878.4	c.-123_-122del		5_prime_UTR_variant	1/4	4		ENSP00000479196

Frequencies

GnomAD3 genomes AF: 0.0456 AC: 6888 AN: 151062 Hom.: 204 Cov.: 30

Gnomad AFR AF: 0.0117

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.0338

Gnomad ASJ AF: 0.0528

Gnomad EAS AF: 0.000780

Gnomad SAS AF: 0.0220

Gnomad FIN AF: 0.0706

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0677

Gnomad OTH AF: 0.0419

GnomAD4 exome AF: 0.0346 AC: 298 AN: 8624 Hom.: 7 AF XY: 0.0326 AC XY: 156 AN XY: 4792

Gnomad4 AFR exome AF: 0.0119

Gnomad4 AMR exome AF: 0.0141

Gnomad4 ASJ exome AF: 0.0407

Gnomad4 EAS exome AF: 0.0133

Gnomad4 SAS exome AF: 0.0215

Gnomad4 FIN exome AF: 0.0208

Gnomad4 NFE exome AF: 0.0488

Gnomad4 OTH exome AF: 0.0209

GnomAD4 genome AF: 0.0456 AC: 6886 AN: 151172 Hom.: 204 Cov.: 30 AF XY: 0.0449 AC XY: 3318 AN XY: 73840

Gnomad4 AFR AF: 0.0117

Gnomad4 AMR AF: 0.0338

Gnomad4 ASJ AF: 0.0528

Gnomad4 EAS AF: 0.000782

Gnomad4 SAS AF: 0.0218

Gnomad4 FIN AF: 0.0706

Gnomad4 NFE AF: 0.0677

Gnomad4 OTH AF: 0.0415

Bravo AF: 0.0419

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

Sep 24, 2019

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs377410821; hg19: chr11-47236153;