11-47214854-C-G

Variant names:

• chr11-47214854-C-G
• rs4237547
• NM_001399874.1:c.-67+180C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001399874.1(DDB2):​c.-67+180C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 493,062 control chromosomes in the GnomAD database, including 90,586 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.50 (22621 hom., cov: 30)
  • Exomes 𝑓: 0.62 (67965 hom.)
• Consequence: DDB2 NM_001399874.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.825
• Publications: 15 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 11-47214854-C-G is Benign according to our data. Variant chr11-47214854-C-G is described in ClinVar as Benign. ClinVar VariationId is 1281860.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001399874.1. 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_001399874.1		c.-67+180C>G		intron	N/A	NP_001386803.1	Q92466-1
	DDB2	NM_001399875.1		c.-65+180C>G		intron	N/A	NP_001386804.1	Q92466-1
	DDB2	NM_001399876.1		c.-67+180C>G		intron	N/A	NP_001386805.1	Q92466-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDB2	ENST00000896514.1		c.-67+111C>G		intron	N/A	ENSP00000566573.1
	DDB2	ENST00000967663.1		c.-66-217C>G		intron	N/A	ENSP00000637722.1
	DDB2	ENST00000967664.1		c.-67+215C>G		intron	N/A	ENSP00000637723.1

Frequencies

GnomAD3 genomes AF: 0.500 AC: 75802 AN: 151660 Hom.: 22617 Cov.: 30

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.695

Gnomad AMR AF: 0.567

Gnomad ASJ AF: 0.721

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.658

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.663

Gnomad OTH AF: 0.566

GnomAD4 exome AF: 0.616 AC: 210263 AN: 341284 Hom.: 67965 Cov.: 3 AF XY: 0.620 AC XY: 111678 AN XY: 179996

African (AFR) AF: 0.171 AC: 1770 AN: 10364

American (AMR) AF: 0.538 AC: 8117 AN: 15094

Ashkenazi Jewish (ASJ) AF: 0.724 AC: 7928 AN: 10954

East Asian (EAS) AF: 0.286 AC: 6428 AN: 22500

South Asian (SAS) AF: 0.642 AC: 27995 AN: 43634

European-Finnish (FIN) AF: 0.586 AC: 9072 AN: 15470

Middle Eastern (MID) AF: 0.653 AC: 941 AN: 1442

European-Non Finnish (NFE) AF: 0.672 AC: 135854 AN: 202042

Other (OTH) AF: 0.615 AC: 12158 AN: 19784

GnomAD4 genome AF: 0.499 AC: 75810 AN: 151778 Hom.: 22621 Cov.: 30 AF XY: 0.498 AC XY: 36934 AN XY: 74146

African (AFR) AF: 0.167 AC: 6904 AN: 41444

American (AMR) AF: 0.566 AC: 8636 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.721 AC: 2502 AN: 3468

East Asian (EAS) AF: 0.301 AC: 1540 AN: 5112

South Asian (SAS) AF: 0.658 AC: 3166 AN: 4812

European-Finnish (FIN) AF: 0.574 AC: 6035 AN: 10516

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.663 AC: 45003 AN: 67866

Other (OTH) AF: 0.572 AC: 1209 AN: 2112

Alfa AF: 0.571 Hom.: 3423

Bravo AF: 0.481

Asia WGS AF: 0.533 AC: 1856 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.7
DANN	Benign	0.41
PhyloP100		-0.82
PromoterAI		-0.11	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4237547; hg19: chr11-47236405;