11-47216270-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.8).
• 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 id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDB2	NM_000107.3	c.128-66C>T		intron_variant		ENST00000256996.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDB2	ENST00000256996.9	c.128-66C>T		intron_variant		1	NM_000107.3	P1

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

GnomAD3 exomes AF: 0.00429 AC: 1073 AN: 249966 Hom.: 2 AF XY: 0.00430 AC XY: 582 AN XY: 135462

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 SAS exome AF: 0.00229

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

Gnomad4 AFR exome AF: 0.00141

Gnomad4 AMR exome AF: 0.00199

Gnomad4 ASJ exome AF: 0.00352

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00252

Gnomad4 FIN exome AF: 0.000769

Gnomad4 NFE exome AF: 0.00895

Gnomad4 OTH exome AF: 0.00640

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

Gnomad4 AFR AF: 0.00149

Gnomad4 AMR AF: 0.00301

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00311

Gnomad4 FIN AF: 0.000850

Gnomad4 NFE AF: 0.00751

Gnomad4 OTH AF: 0.00331

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

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2023

DDB2: BS2 -

not specified Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	4.8
Dann	Benign	0.71

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

Publications

LitVar

Other links and lift over

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