11-47238721-T-C

Variant names:

• chr11-47238721-T-C
• rs2013867
• NM_000107.3:c.1235-79T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.00100
• Publications: 29 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]

ACP2 (HGNC:123): (acid phosphatase 2, lysosomal) The protein encoded by this gene belongs to the histidine acid phosphatase family, which hydrolyze orthophosphoric monoesters to alcohol and phosphate. This protein is localized to the lysosomal membrane, and is chemically and genetically distinct from the red cell acid phosphatase. Mice lacking this gene showed multiple defects, including bone structure alterations, lysosomal storage defects, and an increased tendency towards seizures. An enzymatically-inactive allele of this gene in mice showed severe growth retardation, hair-follicle abnormalities, and an ataxia-like phenotype. Alternatively spliced transcript variants have been found for this gene. A C-terminally extended isoform is also predicted to be produced by the use of an alternative in-frame translation termination codon via a stop codon readthrough mechanism. [provided by RefSeq, Oct 2017]

ACP2 Gene-Disease associations (from GenCC):

• lysosomal acid phosphatase deficiency

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000107.3. 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_000107.3	MANE Select	c.1235-79T>C		intron	N/A	NP_000098.1	Q92466-1
	DDB2	NM_001399874.1		c.1235-79T>C		intron	N/A	NP_001386803.1	Q92466-1
	DDB2	NM_001399875.1		c.1235-79T>C		intron	N/A	NP_001386804.1	Q92466-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDB2	ENST00000256996.9	TSL:1 MANE Select	c.1235-79T>C		intron	N/A	ENSP00000256996.4	Q92466-1
	DDB2	ENST00000378603.7	TSL:1	c.1043-79T>C		intron	N/A	ENSP00000367866.3	Q92466-4
	DDB2	ENST00000378600.7	TSL:1	c.668-79T>C		intron	N/A	ENSP00000367863.3	Q92466-2

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60152 AN: 151178 Hom.: 13165 Cov.: 30

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

African (AFR) AF: 0.540 AC: 17162 AN: 31794

American (AMR) AF: 0.427 AC: 18764 AN: 43992

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 5587 AN: 25368

East Asian (EAS) AF: 0.743 AC: 29031 AN: 39094

South Asian (SAS) AF: 0.462 AC: 38888 AN: 84114

European-Finnish (FIN) AF: 0.407 AC: 20733 AN: 50896

Middle Eastern (MID) AF: 0.272 AC: 1464 AN: 5384

European-Non Finnish (NFE) AF: 0.303 AC: 311847 AN: 1028412

Other (OTH) AF: 0.346 AC: 19709 AN: 57014

GnomAD4 genome AF: 0.398 AC: 60194 AN: 151296 Hom.: 13175 Cov.: 30 AF XY: 0.407 AC XY: 30129 AN XY: 73962

African (AFR) AF: 0.537 AC: 22158 AN: 41268

American (AMR) AF: 0.361 AC: 5485 AN: 15186

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 777 AN: 3464

East Asian (EAS) AF: 0.750 AC: 3838 AN: 5118

South Asian (SAS) AF: 0.468 AC: 2241 AN: 4792

European-Finnish (FIN) AF: 0.428 AC: 4482 AN: 10474

Middle Eastern (MID) AF: 0.271 AC: 78 AN: 288

European-Non Finnish (NFE) AF: 0.300 AC: 20308 AN: 67700

Other (OTH) AF: 0.336 AC: 706 AN: 2102

Alfa AF: 0.369 Hom.: 5919

Bravo AF: 0.396

Asia WGS AF: 0.548 AC: 1904 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.3
DANN	Benign	0.39
PhyloP100		-0.0010
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2013867; hg19: chr11-47260272; COSMIC: COSV57041179; COSMIC: COSV57041179;