Variant rs326222 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.1189-21T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.654 in 1,610,336 control chromosomes in the GnomAD database, including 354,776 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.58 ( 27322 hom., cov: 31)

Exomes 𝑓: 0.66 ( 327454 hom. )

Consequence

DDB2
NM_000107.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.151

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:

DDB2 (HGNC:):

DDB2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 11-47238117-T-C is Benign according to our data. Variant chr11-47238117-T-C is described in ClinVar as [Benign]. Clinvar id is 1237094.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDB2	NM_000107.3 linkuse as main transcript	c.1189-21T>C		intron_variant		ENST00000256996.9	NP_000098.1	Q92466-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDB2	ENST00000256996.9 linkuse as main transcript	c.1189-21T>C		intron_variant		1	NM_000107.3	ENSP00000256996.4		Q92466-1

Frequencies

GnomAD3 genomes

AF:

0.580

AC:

88090

AN:

151896

Hom.:

27301

Cov.:

show subpopulations

Gnomad AFR

AF:

0.385

Gnomad AMI

AF:

0.867

Gnomad AMR

AF:

0.628

Gnomad ASJ

AF:

0.773

Gnomad EAS

AF:

0.255

Gnomad SAS

AF:

0.534

Gnomad FIN

AF:

0.573

Gnomad MID

AF:

0.709

Gnomad NFE

AF:

0.700

Gnomad OTH

AF:

0.644

GnomAD3 exomes

AF:

0.599

AC:

148264

AN:

247400

Hom.:

46989

AF XY:

0.609

AC XY:

81455

AN XY:

133678

show subpopulations

Gnomad AFR exome

AF:

0.376

Gnomad AMR exome

AF:

0.554

Gnomad ASJ exome

AF:

0.778

Gnomad EAS exome

AF:

0.241

Gnomad SAS exome

AF:

0.538

Gnomad FIN exome

AF:

0.580

Gnomad NFE exome

AF:

0.704

Gnomad OTH exome

AF:

0.675

GnomAD4 exome

AF:

0.662

AC:

965777

AN:

1458322

Hom.:

327454

Cov.:

AF XY:

0.661

AC XY:

479460

AN XY:

725356

show subpopulations

Gnomad4 AFR exome

AF:

0.381

Gnomad4 AMR exome

AF:

0.566

Gnomad4 ASJ exome

AF:

0.780

Gnomad4 EAS exome

AF:

0.258

Gnomad4 SAS exome

AF:

0.538

Gnomad4 FIN exome

AF:

0.590

Gnomad4 NFE exome

AF:

0.700

Gnomad4 OTH exome

AF:

0.651

GnomAD4 genome

AF:

0.580

AC:

88160

AN:

152014

Hom.:

27322

Cov.:

AF XY:

0.571

AC XY:

42437

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.385

Gnomad4 AMR

AF:

0.628

Gnomad4 ASJ

AF:

0.773

Gnomad4 EAS

AF:

0.254

Gnomad4 SAS

AF:

0.535

Gnomad4 FIN

AF:

0.573

Gnomad4 NFE

AF:

0.700

Gnomad4 OTH

AF:

0.648

Alfa

AF:

0.651

Hom.:

9049

Bravo

AF:

0.576

Asia WGS

AF:

0.445

AC:

1549

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

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	Jan 10, 2019	- -

Xeroderma pigmentosum, group E

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

7.5

DANN

Benign

0.68

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

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