11-47216129-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000107.3(DDB2):c.128-207T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 746,076 control chromosomes in the GnomAD database, including 5,741 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.10 (997 hom., cov: 32)
  • Exomes 𝑓: 0.12 (4744 hom.)
• Consequence: DDB2 NM_000107.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.723

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=-0.79).
• BP6: Variant 11-47216129-T-C is Benign according to our data. Variant chr11-47216129-T-C is described in ClinVar as [Benign]. Clinvar id is 1276638.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDB2	NM_000107.3	c.128-207T>C		intron_variant		ENST00000256996.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDB2	ENST00000256996.9	c.128-207T>C		intron_variant		1	NM_000107.3	P1

Frequencies

GnomAD3 genomes AF: 0.0997 AC: 15168 AN: 152074 Hom.: 992 Cov.: 32

Gnomad AFR AF: 0.0261

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.0830

Gnomad EAS AF: 0.0364

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.117

GnomAD4 exome AF: 0.120 AC: 71357 AN: 593882 Hom.: 4744 Cov.: 7 AF XY: 0.119 AC XY: 38406 AN XY: 321430

Gnomad4 AFR exome AF: 0.0259

Gnomad4 AMR exome AF: 0.163

Gnomad4 ASJ exome AF: 0.0882

Gnomad4 EAS exome AF: 0.0262

Gnomad4 SAS exome AF: 0.112

Gnomad4 FIN exome AF: 0.147

Gnomad4 NFE exome AF: 0.130

Gnomad4 OTH exome AF: 0.121

GnomAD4 genome AF: 0.0997 AC: 15177 AN: 152194 Hom.: 997 Cov.: 32 AF XY: 0.0995 AC XY: 7401 AN XY: 74416

Gnomad4 AFR AF: 0.0260

Gnomad4 AMR AF: 0.146

Gnomad4 ASJ AF: 0.0830

Gnomad4 EAS AF: 0.0357

Gnomad4 SAS AF: 0.113

Gnomad4 FIN AF: 0.143

Gnomad4 NFE AF: 0.130

Gnomad4 OTH AF: 0.125

Alfa AF: 0.122 Hom.: 801

Bravo AF: 0.0969

Asia WGS AF: 0.0960 AC: 336 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 10, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	11
Dann	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs2291120; hg19: chr11-47237680;