11-47232500-G-C

Position:

• chr11-47232500-G-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.457-314G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.732 in 150,114 control chromosomes in the GnomAD database, including 41,434 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.73 (41434 hom., cov: 27)
• Consequence: DDB2 NM_000107.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -5.36

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BP6: Variant 11-47232500-G-C is Benign according to our data. Variant chr11-47232500-G-C is described in ClinVar as [Benign]. Clinvar id is 1245123.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.837 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDB2	NM_000107.3	c.457-314G>C		intron_variant		ENST00000256996.9	NP_000098.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDB2	ENST00000256996.9	c.457-314G>C		intron_variant		1	NM_000107.3	ENSP00000256996.4

Frequencies

GnomAD3 genomes AF: 0.732 AC: 109773 AN: 150006 Hom.: 41401 Cov.: 27

Gnomad AFR AF: 0.576

Gnomad AMI AF: 0.919

Gnomad AMR AF: 0.725

Gnomad ASJ AF: 0.867

Gnomad EAS AF: 0.361

Gnomad SAS AF: 0.767

Gnomad FIN AF: 0.717

Gnomad MID AF: 0.824

Gnomad NFE AF: 0.843

Gnomad OTH AF: 0.774

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.732 AC: 109859 AN: 150114 Hom.: 41434 Cov.: 27 AF XY: 0.723 AC XY: 52948 AN XY: 73220

Gnomad4 AFR AF: 0.576

Gnomad4 AMR AF: 0.725

Gnomad4 ASJ AF: 0.867

Gnomad4 EAS AF: 0.360

Gnomad4 SAS AF: 0.768

Gnomad4 FIN AF: 0.717

Gnomad4 NFE AF: 0.842

Gnomad4 OTH AF: 0.778

Alfa AF: 0.726 Hom.: 2321

Bravo AF: 0.717

Asia WGS AF: 0.646 AC: 2247 AN: 3476

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

Aug 21, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.12
DANN	Benign	0.56

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: rs830083; hg19: chr11-47254051;