NM_000107.3:c.456+1890A>T

Variant names:

• chr11-47218939-A-T
• rs10742797
• NM_000107.3:c.456+1890A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000107.3(DDB2):​c.456+1890A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 151,942 control chromosomes in the GnomAD database, including 7,692 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.31 (7692 hom., cov: 32)
• Consequence: DDB2 NM_000107.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.491
• Publications: 12 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDB2	NM_000107.3	c.456+1890A>T		intron_variant	Intron 3 of 9	ENST00000256996.9	NP_000098.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDB2	ENST00000256996.9	c.456+1890A>T		intron_variant	Intron 3 of 9	1	NM_000107.3	ENSP00000256996.4

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46580 AN: 151824 Hom.: 7677 Cov.: 32

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.643

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.275

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

GnomAD4 genome AF: 0.307 AC: 46642 AN: 151942 Hom.: 7692 Cov.: 32 AF XY: 0.314 AC XY: 23353 AN XY: 74264

African (AFR) AF: 0.354 AC: 14676 AN: 41404

American (AMR) AF: 0.333 AC: 5083 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 665 AN: 3464

East Asian (EAS) AF: 0.645 AC: 3341 AN: 5182

South Asian (SAS) AF: 0.292 AC: 1408 AN: 4822

European-Finnish (FIN) AF: 0.365 AC: 3839 AN: 10532

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.246 AC: 16737 AN: 67960

Other (OTH) AF: 0.271 AC: 572 AN: 2114

Alfa AF: 0.283 Hom.: 790

Bravo AF: 0.312

Asia WGS AF: 0.387 AC: 1344 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.31
DANN	Benign	0.28
PhyloP100		-0.49
Mutation Taster		=100/0	polymorphism (auto)

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: rs10742797; hg19: chr11-47240490;