11-47232500-G-C

Variant names:

• chr11-47232500-G-C
• rs830083
• NM_000107.3:c.457-314G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 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=-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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000107.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDB2	NM_000107.3	MANE Select	c.457-314G>C		intron	N/A	NP_000098.1
	DDB2	NM_001399874.1		c.457-314G>C		intron	N/A	NP_001386803.1
	DDB2	NM_001399875.1		c.457-314G>C		intron	N/A	NP_001386804.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDB2	ENST00000256996.9	TSL:1 MANE Select	c.457-314G>C		intron	N/A	ENSP00000256996.4
	DDB2	ENST00000378603.7	TSL:1	c.265-314G>C		intron	N/A	ENSP00000367866.3
	DDB2	ENST00000378600.7	TSL:1	c.457-5337G>C		intron	N/A	ENSP00000367863.3

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

African (AFR) AF: 0.576 AC: 23387 AN: 40592

American (AMR) AF: 0.725 AC: 10924 AN: 15068

Ashkenazi Jewish (ASJ) AF: 0.867 AC: 3000 AN: 3462

East Asian (EAS) AF: 0.360 AC: 1801 AN: 5000

South Asian (SAS) AF: 0.768 AC: 3655 AN: 4762

European-Finnish (FIN) AF: 0.717 AC: 7277 AN: 10148

Middle Eastern (MID) AF: 0.828 AC: 240 AN: 290

European-Non Finnish (NFE) AF: 0.842 AC: 57113 AN: 67792

Other (OTH) AF: 0.778 AC: 1624 AN: 2088

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

Aug 21, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.12
DANN	Benign	0.56
PhyloP100		-5.4
Mutation Taster		=11/89	disease causing (long InDel)

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

Other links and lift over

dbSNP: rs830083; hg19: chr11-47254051;