11-47214854-C-G

Position:

• chr11-47214854-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001399874.1(DDB2):​c.-67+180C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 493,062 control chromosomes in the GnomAD database, including 90,586 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.50 (22621 hom., cov: 30)
  • Exomes 𝑓: 0.62 (67965 hom.)
• Consequence: DDB2 NM_001399874.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.825

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 11-47214854-C-G is Benign according to our data. Variant chr11-47214854-C-G is described in ClinVar as [Benign]. Clinvar id is 1281860.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDB2	NM_001399874.1	c.-67+180C>G		intron_variant			NP_001386803.1
DDB2	NM_001399875.1	c.-65+180C>G		intron_variant			NP_001386804.1
DDB2	NM_001399876.1	c.-67+180C>G		intron_variant			NP_001386805.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDB2	ENST00000614825.4	c.-65+180C>G		intron_variant		3		ENSP00000483718
DDB2	ENST00000622878.4	c.-67+180C>G		intron_variant		4		ENSP00000479196

Frequencies

GnomAD3 genomes AF: 0.500 AC: 75802 AN: 151660 Hom.: 22617 Cov.: 30

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.695

Gnomad AMR AF: 0.567

Gnomad ASJ AF: 0.721

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.658

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.663

Gnomad OTH AF: 0.566

GnomAD4 exome AF: 0.616 AC: 210263 AN: 341284 Hom.: 67965 Cov.: 3 AF XY: 0.620 AC XY: 111678 AN XY: 179996

Gnomad4 AFR exome AF: 0.171

Gnomad4 AMR exome AF: 0.538

Gnomad4 ASJ exome AF: 0.724

Gnomad4 EAS exome AF: 0.286

Gnomad4 SAS exome AF: 0.642

Gnomad4 FIN exome AF: 0.586

Gnomad4 NFE exome AF: 0.672

Gnomad4 OTH exome AF: 0.615

GnomAD4 genome AF: 0.499 AC: 75810 AN: 151778 Hom.: 22621 Cov.: 30 AF XY: 0.498 AC XY: 36934 AN XY: 74146

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.566

Gnomad4 ASJ AF: 0.721

Gnomad4 EAS AF: 0.301

Gnomad4 SAS AF: 0.658

Gnomad4 FIN AF: 0.574

Gnomad4 NFE AF: 0.663

Gnomad4 OTH AF: 0.572

Alfa AF: 0.571 Hom.: 3423

Bravo AF: 0.481

Asia WGS AF: 0.533 AC: 1856 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 10, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.7
DANN	Benign	0.41

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4237547; hg19: chr11-47236405;