Variant 11-47238721-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000107.3(DDB2):c.1235-79T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 1,517,364 control chromosomes in the GnomAD database, including 98,198 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 13175 hom., cov: 30)

Exomes 𝑓: 0.34 ( 85023 hom. )

Consequence

DDB2
NM_000107.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.00100

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 11-47238721-T-C is Benign according to our data. Variant chr11-47238721-T-C is described in ClinVar as [Benign]. Clinvar id is 1288463.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDB2	NM_000107.3 linkuse as main transcript	c.1235-79T>C		intron_variant		ENST00000256996.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDB2	ENST00000256996.9 linkuse as main transcript	c.1235-79T>C		intron_variant		1	NM_000107.3	P1	Q92466-1

Frequencies

GnomAD3 genomes

AF:

0.398

AC:

60152

AN:

151178

Hom.:

13165

Cov.:

show subpopulations

Gnomad AFR

AF:

0.537

Gnomad AMI

AF:

0.134

Gnomad AMR

AF:

0.361

Gnomad ASJ

AF:

0.224

Gnomad EAS

AF:

0.749

Gnomad SAS

AF:

0.468

Gnomad FIN

AF:

0.428

Gnomad MID

AF:

0.268

Gnomad NFE

AF:

0.300

Gnomad OTH

AF:

0.340

GnomAD4 exome

AF:

0.339

AC:

463185

AN:

1366068

Hom.:

85023

AF XY:

0.340

AC XY:

233071

AN XY:

684706

show subpopulations

Gnomad4 AFR exome

AF:

0.540

Gnomad4 AMR exome

AF:

0.427

Gnomad4 ASJ exome

AF:

0.220

Gnomad4 EAS exome

AF:

0.743

Gnomad4 SAS exome

AF:

0.462

Gnomad4 FIN exome

AF:

0.407

Gnomad4 NFE exome

AF:

0.303

Gnomad4 OTH exome

AF:

0.346

GnomAD4 genome

AF:

0.398

AC:

60194

AN:

151296

Hom.:

13175

Cov.:

AF XY:

0.407

AC XY:

30129

AN XY:

73962

show subpopulations

Gnomad4 AFR

AF:

0.537

Gnomad4 AMR

AF:

0.361

Gnomad4 ASJ

AF:

0.224

Gnomad4 EAS

AF:

0.750

Gnomad4 SAS

AF:

0.468

Gnomad4 FIN

AF:

0.428

Gnomad4 NFE

AF:

0.300

Gnomad4 OTH

AF:

0.336

Alfa

AF:

0.343

Hom.:

3358

Bravo

AF:

0.396

Asia WGS

AF:

0.548

AC:

1904

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 02, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

6.3

DANN

Benign

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over