rs56310830

chr11-47216252-T-G

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.128-84T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00127 in 1,601,008 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0062 (13 hom., cov: 32)
  • Exomes 𝑓: 0.00075 (7 hom.)
• Consequence: DDB2 NM_000107.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1 O:1
• Conservation: PhyloP100: -0.214

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=-0.71).
• BP6: Variant 11-47216252-T-G is Benign according to our data. Variant chr11-47216252-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 135511.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00624 (951/152290) while in subpopulation AFR AF= 0.0218 (904/41558). AF 95% confidence interval is 0.0206. There are 13 homozygotes in gnomad4. There are 456 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDB2	NM_000107.3	c.128-84T>G		intron_variant		ENST00000256996.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDB2	ENST00000256996.9	c.128-84T>G		intron_variant		1	NM_000107.3	P1

Frequencies

GnomAD3 genomes AF: 0.00624 AC: 950 AN: 152172 Hom.: 13 Cov.: 32

Gnomad AFR AF: 0.0218

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00196

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00527

GnomAD3 exomes AF: 0.00168 AC: 418 AN: 248592 Hom.: 6 AF XY: 0.00101 AC XY: 136 AN XY: 135116

Gnomad AFR exome AF: 0.0231

Gnomad AMR exome AF: 0.00104

Gnomad ASJ exome AF: 0.000796

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000654

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000447

Gnomad OTH exome AF: 0.000658

GnomAD4 exome AF: 0.000752 AC: 1090 AN: 1448718 Hom.: 7 Cov.: 28 AF XY: 0.000611 AC XY: 441 AN XY: 721472

Gnomad4 AFR exome AF: 0.0254

Gnomad4 AMR exome AF: 0.00123

Gnomad4 ASJ exome AF: 0.000882

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000467

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000345

Gnomad4 OTH exome AF: 0.00188

GnomAD4 genome AF: 0.00624 AC: 951 AN: 152290 Hom.: 13 Cov.: 32 AF XY: 0.00612 AC XY: 456 AN XY: 74472

Gnomad4 AFR AF: 0.0218

Gnomad4 AMR AF: 0.00196

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00521

Alfa AF: 0.00399 Hom.: 2

Bravo AF: 0.00735

Asia WGS AF: 0.000866 AC: 3 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

GeneDx

Dec 10, 2020

- -

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	-0.71
Cadd	Benign	5.3
Dann	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs56310830; hg19: chr11-47237803;