chr11-47216252-T-G

Variant names:

• chr11-47216252-T-G
• rs56310830
• NM_000107.3:c.128-84T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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), Genomics England PanelApp, ClinGen
• 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=-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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 13 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDB2	NM_000107.3	MANE Select	c.128-84T>G		intron	N/A	NP_000098.1	Q92466-1
	DDB2	NM_001399874.1		c.128-84T>G		intron	N/A	NP_001386803.1	Q92466-1
	DDB2	NM_001399875.1		c.128-84T>G		intron	N/A	NP_001386804.1	Q92466-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDB2	ENST00000256996.9	TSL:1 MANE Select	c.128-84T>G		intron	N/A	ENSP00000256996.4	Q92466-1
	DDB2	ENST00000378603.7	TSL:1	c.128-84T>G		intron	N/A	ENSP00000367866.3	Q92466-4
	DDB2	ENST00000378600.7	TSL:1	c.128-84T>G		intron	N/A	ENSP00000367863.3	Q92466-2

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

GnomAD2 exomes AF: 0.00168 AC: 418 AN: 248592 AF XY: 0.00101

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 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

African (AFR) AF: 0.0254 AC: 846 AN: 33264

American (AMR) AF: 0.00123 AC: 55 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.000882 AC: 23 AN: 26070

East Asian (EAS) AF: 0.00 AC: 0 AN: 39640

South Asian (SAS) AF: 0.0000467 AC: 4 AN: 85680

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53060

Middle Eastern (MID) AF: 0.00191 AC: 11 AN: 5752

European-Non Finnish (NFE) AF: 0.0000345 AC: 38 AN: 1100536

Other (OTH) AF: 0.00188 AC: 113 AN: 60008

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

African (AFR) AF: 0.0218 AC: 904 AN: 41558

American (AMR) AF: 0.00196 AC: 30 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68024

Other (OTH) AF: 0.00521 AC: 11 AN: 2110

Alfa AF: 0.0100 Hom.: 4

Bravo AF: 0.00735

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_noAF	Benign	-0.71
CADD	Benign	5.3
DANN	Benign	0.75
PhyloP100		-0.21
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs56310830; hg19: chr11-47237803;