rs4647707
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000107.3(DDB2):c.-120G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0181 in 1,493,168 control chromosomes in the GnomAD database, including 4,020 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.092 ( 2133 hom., cov: 31)
Exomes 𝑓: 0.0097 ( 1887 hom. )
Consequence
DDB2
NM_000107.3 5_prime_UTR
NM_000107.3 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.284
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]
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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=-0.67).
BP6
?
Variant 11-47215017-G-A is Benign according to our data. Variant chr11-47215017-G-A is described in ClinVar as [Benign]. Clinvar id is 304913.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DDB2 | NM_000107.3 | c.-120G>A | 5_prime_UTR_variant | 1/10 | ENST00000256996.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DDB2 | ENST00000256996.9 | c.-120G>A | 5_prime_UTR_variant | 1/10 | 1 | NM_000107.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0920 AC: 13978AN: 152014Hom.: 2132 Cov.: 31
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GnomAD4 exome AF: 0.00974 AC: 13060AN: 1341036Hom.: 1887 Cov.: 20 AF XY: 0.00842 AC XY: 5664AN XY: 673040
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GnomAD4 genome ? AF: 0.0920 AC: 13997AN: 152132Hom.: 2133 Cov.: 31 AF XY: 0.0891 AC XY: 6625AN XY: 74388
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Xeroderma pigmentosum, group E Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 28, 2019 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at