11-47216270-C-T

Variant names:

• chr11-47216270-C-T
• rs186870004
• NM_000107.3:c.128-66C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_000107.3(DDB2):​c.128-66C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00715 in 1,612,136 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0047 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0074 (44 hom.)
• Consequence: DDB2 NM_000107.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1 O:1
• Conservation: PhyloP100: -0.856
• Publications: 2 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=-0.8).
• BP6: Variant 11-47216270-C-T is Benign according to our data. Variant chr11-47216270-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 135512.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00472 (719/152230) while in subpopulation NFE AF = 0.00751 (511/68020). AF 95% confidence interval is 0.00697. There are 5 homozygotes in GnomAd4. There are 321 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDB2	NM_000107.3	c.128-66C>T		intron_variant	Intron 1 of 9	ENST00000256996.9	NP_000098.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDB2	ENST00000256996.9	c.128-66C>T		intron_variant	Intron 1 of 9	1	NM_000107.3	ENSP00000256996.4

Frequencies

GnomAD3 genomes AF: 0.00473 AC: 719 AN: 152112 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00150

Gnomad AMI AF: 0.0681

Gnomad AMR AF: 0.00301

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00311

Gnomad FIN AF: 0.000850

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00751

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00429 AC: 1073 AN: 249966 AF XY: 0.00430

Gnomad AFR exome AF: 0.00131

Gnomad AMR exome AF: 0.00205

Gnomad ASJ exome AF: 0.00259

Gnomad EAS exome AF: 0.0000545

Gnomad FIN exome AF: 0.000694

Gnomad NFE exome AF: 0.00749

Gnomad OTH exome AF: 0.00410

GnomAD4 exome AF: 0.00741 AC: 10815 AN: 1459906 Hom.: 44 Cov.: 30 AF XY: 0.00713 AC XY: 5179 AN XY: 726364

African (AFR) AF: 0.00141 AC: 47 AN: 33446

American (AMR) AF: 0.00199 AC: 89 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00352 AC: 92 AN: 26128

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39686

South Asian (SAS) AF: 0.00252 AC: 217 AN: 86084

European-Finnish (FIN) AF: 0.000769 AC: 41 AN: 53288

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00895 AC: 9942 AN: 1110446

Other (OTH) AF: 0.00640 AC: 386 AN: 60344

GnomAD4 genome AF: 0.00472 AC: 719 AN: 152230 Hom.: 5 Cov.: 32 AF XY: 0.00431 AC XY: 321 AN XY: 74422

African (AFR) AF: 0.00149 AC: 62 AN: 41534

American (AMR) AF: 0.00301 AC: 46 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00311 AC: 15 AN: 4820

European-Finnish (FIN) AF: 0.000850 AC: 9 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00751 AC: 511 AN: 68020

Other (OTH) AF: 0.00331 AC: 7 AN: 2114

Alfa AF: 0.00531 Hom.: 0

Bravo AF: 0.00490

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

DDB2: BS2 -

not specified Other:1

Sep 19, 2013

ITMI

Significance: not provided

Review Status: no classification provided

Collection Method: reference population

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.8
DANN	Benign	0.71
PhyloP100		-0.86
Mutation Taster		=100/0	polymorphism

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: rs186870004; hg19: chr11-47237821; COSMIC: COSV57039930; COSMIC: COSV57039930;