Genetic Variant DDB2:c.-125_-122dupGAGA (chr11-47214602-A-AAGAG) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001399874.1(DDB2):c.-125_-122dupGAGA variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000199 in 151,096 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DDB2
NM_001399874.1 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0470

Publications

1 publications found

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 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

DDB2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
DDB2	NM_001399874.1	c.-125_-122dupGAGA	5_prime_UTR	Exon 1 of 11	NP_001386803.1	Q92466-1
DDB2	NM_001399875.1	c.-123_-120dupGAGA	5_prime_UTR	Exon 1 of 11	NP_001386804.1	Q92466-1
DDB2	NM_001399876.1	c.-125_-122dupGAGA	5_prime_UTR	Exon 1 of 7	NP_001386805.1	Q92466-2

Ensembl Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein
DDB2	ENST00000896514.1	c.-194_-191dupGAGA	5_prime_UTR	Exon 1 of 11	ENSP00000566573.1
DDB2	ENST00000967664.1	c.-90_-87dupGAGA	5_prime_UTR	Exon 1 of 11	ENSP00000637723.1
DDB2	ENST00000967665.1	c.-125_-122dupGAGA	5_prime_UTR	Exon 1 of 11	ENSP00000637724.1

Frequencies

GnomAD3 genomes

AF:

0.0000199

AC:

AN:

151096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000295

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

8760

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

4866

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

1224

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

176

East Asian (EAS)

AF:

0.00

AC:

AN:

616

South Asian (SAS)

AF:

0.00

AC:

AN:

1504

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

4650

Other (OTH)

AF:

0.00

AC:

AN:

430

GnomAD4 genome

AF:

0.0000199

AC:

AN:

151096

Hom.:

Cov.:

AF XY:

0.0000271

AC XY:

AN XY:

73738

show subpopulations

African (AFR)

AF:

0.0000243

AC:

AN:

41110

American (AMR)

AF:

0.00

AC:

AN:

15140

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5130

South Asian (SAS)

AF:

0.00

AC:

AN:

4774

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000295

AC:

AN:

67768

Other (OTH)

AF:

0.00

AC:

AN:

2076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.047

Splicing

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

Publications

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11-47214602-AAGAGAG-AAGAGAGAGAG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over