11-47214602-AAGAGAG-AAG

Variant names:

• chr11-47214602-AAGAG-AA
• NM_001399874.1:c.-137_-135delGAG

Variant summary

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

The NM_001399874.1(DDB2):​c.-137_-135delGAG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DDB2 NM_001399874.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.06
• Publications: 0 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), Genomics England PanelApp, ClinGen
• xeroderma pigmentosum

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDB2	NM_001399874.1		c.-137_-135delGAG		5_prime_UTR	Exon 1 of 11	NP_001386803.1	Q92466-1
	DDB2	NM_001399875.1		c.-135_-133delGAG		5_prime_UTR	Exon 1 of 11	NP_001386804.1	Q92466-1
	DDB2	NM_001399876.1		c.-137_-135delGAG		5_prime_UTR	Exon 1 of 7	NP_001386805.1	Q92466-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDB2	ENST00000896514.1		c.-206_-204delGAG		5_prime_UTR	Exon 1 of 11	ENSP00000566573.1
	DDB2	ENST00000967664.1		c.-102_-100delGAG		5_prime_UTR	Exon 1 of 11	ENSP00000637723.1
	DDB2	ENST00000967665.1		c.-137_-135delGAG		5_prime_UTR	Exon 1 of 11	ENSP00000637724.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 5930 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 3228

African (AFR) AF: 0.00 AC: 0 AN: 66

American (AMR) AF: 0.00 AC: 0 AN: 850

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 130

East Asian (EAS) AF: 0.00 AC: 0 AN: 442

South Asian (SAS) AF: 0.00 AC: 0 AN: 1082

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 10

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 3010

Other (OTH) AF: 0.00 AC: 0 AN: 306

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr11-47236153;