11-47237713-G-C

Variant names:

• chr11-47237713-G-C
• rs3781620
• NM_000107.3:c.1024-124G>C

Variant summary

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

The NM_000107.3(DDB2):​c.1024-124G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 961,424 control chromosomes in the GnomAD database, including 30,249 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.27 (6835 hom., cov: 30)
  • Exomes 𝑓: 0.21 (23414 hom.)
• Consequence: DDB2 NM_000107.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.205
• Publications: 11 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), ClinGen, Genomics England PanelApp
• 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=-0.88).
• BP6: Variant 11-47237713-G-C is Benign according to our data. Variant chr11-47237713-G-C is described in ClinVar as Benign. ClinVar VariationId is 1249280.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDB2	NM_000107.3	c.1024-124G>C		intron_variant	Intron 7 of 9	ENST00000256996.9	NP_000098.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDB2	ENST00000256996.9	c.1024-124G>C		intron_variant	Intron 7 of 9	1	NM_000107.3	ENSP00000256996.4

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40515 AN: 151694 Hom.: 6830 Cov.: 30

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.0813

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.648

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.222

GnomAD4 exome AF: 0.207 AC: 167401 AN: 809612 Hom.: 23414 Cov.: 11 AF XY: 0.205 AC XY: 86996 AN XY: 424500

African (AFR) AF: 0.411 AC: 8640 AN: 21002

American (AMR) AF: 0.366 AC: 13800 AN: 37674

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 2780 AN: 21492

East Asian (EAS) AF: 0.655 AC: 23079 AN: 35212

South Asian (SAS) AF: 0.234 AC: 16307 AN: 69678

European-Finnish (FIN) AF: 0.264 AC: 11572 AN: 43820

Middle Eastern (MID) AF: 0.164 AC: 519 AN: 3164

European-Non Finnish (NFE) AF: 0.154 AC: 82856 AN: 538826

Other (OTH) AF: 0.203 AC: 7848 AN: 38744

GnomAD4 genome AF: 0.267 AC: 40545 AN: 151812 Hom.: 6835 Cov.: 30 AF XY: 0.277 AC XY: 20522 AN XY: 74162

African (AFR) AF: 0.413 AC: 17084 AN: 41370

American (AMR) AF: 0.275 AC: 4184 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 455 AN: 3470

East Asian (EAS) AF: 0.649 AC: 3340 AN: 5146

South Asian (SAS) AF: 0.233 AC: 1122 AN: 4818

European-Finnish (FIN) AF: 0.297 AC: 3116 AN: 10506

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.157 AC: 10662 AN: 67952

Other (OTH) AF: 0.219 AC: 461 AN: 2108

Alfa AF: 0.108 Hom.: 149

Bravo AF: 0.275

Asia WGS AF: 0.346 AC: 1201 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 02, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.5
DANN	Benign	0.66
PhyloP100		0.20
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs3781620; hg19: chr11-47259264; COSMIC: COSV57036996; COSMIC: COSV57036996;