rs1050244

Variant names:

• chr11-47238926-C-T
• rs1050244
• NM_000107.3:c.*77C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-47238926-C-T
• chr11-47238926-C-A

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.*77C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0398 in 1,531,978 control chromosomes in the GnomAD database, including 1,636 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.034 (122 hom., cov: 31)
  • Exomes 𝑓: 0.040 (1514 hom.)
• Consequence: DDB2 NM_000107.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.21
• Publications: 13 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=-0.8).
• BP6: Variant 11-47238926-C-T is Benign according to our data. Variant chr11-47238926-C-T is described in ClinVar as Benign. ClinVar VariationId is 304930.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.11 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.*77C>T		3_prime_UTR	Exon 10 of 10	NP_000098.1	Q92466-1
	DDB2	NM_001399874.1		c.*77C>T		3_prime_UTR	Exon 11 of 11	NP_001386803.1	Q92466-1
	DDB2	NM_001399875.1		c.*77C>T		3_prime_UTR	Exon 11 of 11	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.*77C>T		3_prime_UTR	Exon 10 of 10	ENSP00000256996.4	Q92466-1
	DDB2	ENST00000896514.1		c.*77C>T		3_prime_UTR	Exon 11 of 11	ENSP00000566573.1
	DDB2	ENST00000967663.1		c.*77C>T		3_prime_UTR	Exon 11 of 11	ENSP00000637722.1

Frequencies

GnomAD3 genomes AF: 0.0342 AC: 5179 AN: 151630 Hom.: 124 Cov.: 31

Gnomad AFR AF: 0.0226

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0167

Gnomad ASJ AF: 0.0156

Gnomad EAS AF: 0.0428

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.0468

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0377

Gnomad OTH AF: 0.0318

GnomAD4 exome AF: 0.0405 AC: 55857 AN: 1380230 Hom.: 1514 Cov.: 21 AF XY: 0.0429 AC XY: 29580 AN XY: 689484

African (AFR) AF: 0.0230 AC: 735 AN: 31942

American (AMR) AF: 0.0140 AC: 594 AN: 42516

Ashkenazi Jewish (ASJ) AF: 0.0126 AC: 320 AN: 25348

East Asian (EAS) AF: 0.0352 AC: 1364 AN: 38792

South Asian (SAS) AF: 0.113 AC: 9462 AN: 83758

European-Finnish (FIN) AF: 0.0499 AC: 2483 AN: 49764

Middle Eastern (MID) AF: 0.0259 AC: 113 AN: 4364

European-Non Finnish (NFE) AF: 0.0367 AC: 38376 AN: 1046200

Other (OTH) AF: 0.0419 AC: 2410 AN: 57546

GnomAD4 genome AF: 0.0341 AC: 5176 AN: 151748 Hom.: 122 Cov.: 31 AF XY: 0.0358 AC XY: 2656 AN XY: 74114

African (AFR) AF: 0.0227 AC: 940 AN: 41392

American (AMR) AF: 0.0166 AC: 253 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.0156 AC: 54 AN: 3466

East Asian (EAS) AF: 0.0421 AC: 216 AN: 5130

South Asian (SAS) AF: 0.118 AC: 567 AN: 4802

European-Finnish (FIN) AF: 0.0468 AC: 492 AN: 10504

Middle Eastern (MID) AF: 0.0137 AC: 4 AN: 292

European-Non Finnish (NFE) AF: 0.0377 AC: 2562 AN: 67936

Other (OTH) AF: 0.0319 AC: 67 AN: 2098

Alfa AF: 0.0339 Hom.: 65

Bravo AF: 0.0289

Asia WGS AF: 0.117 AC: 407 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Xeroderma pigmentosum, group E (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	13
DANN	Benign	0.56
PhyloP100		1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs1050244; hg19: chr11-47260477; COSMIC: COSV104563737;