11-47243341-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_001610.4(ACP2):c.773-20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00273 in 1,609,802 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0023 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0028 (15 hom.)
• Consequence: ACP2 NM_001610.4 intron
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -2.35

Genes affected

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]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 11-47243341-G-A is Benign according to our data. Variant chr11-47243341-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 558905.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACP2	NM_001610.4	c.773-20C>T		intron_variant		ENST00000672073.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACP2	ENST00000672073.1	c.773-20C>T		intron_variant			NM_001610.4	P1

Frequencies

GnomAD3 genomes AF: 0.00231 AC: 351 AN: 152194 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000386

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00245

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00337

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00263 AC: 654 AN: 249108 Hom.: 0 AF XY: 0.00261 AC XY: 352 AN XY: 134854

Gnomad AFR exome AF: 0.000124

Gnomad AMR exome AF: 0.00180

Gnomad ASJ exome AF: 0.00542

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000852

Gnomad FIN exome AF: 0.00246

Gnomad NFE exome AF: 0.00389

Gnomad OTH exome AF: 0.00330

GnomAD4 exome AF: 0.00277 AC: 4039 AN: 1457490 Hom.: 15 Cov.: 30 AF XY: 0.00280 AC XY: 2032 AN XY: 725334

Gnomad4 AFR exome AF: 0.000629

Gnomad4 AMR exome AF: 0.00190

Gnomad4 ASJ exome AF: 0.00426

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000743

Gnomad4 FIN exome AF: 0.00264

Gnomad4 NFE exome AF: 0.00308

Gnomad4 OTH exome AF: 0.00306

GnomAD4 genome AF: 0.00230 AC: 351 AN: 152312 Hom.: 2 Cov.: 33 AF XY: 0.00192 AC XY: 143 AN XY: 74466

Gnomad4 AFR AF: 0.000385

Gnomad4 AMR AF: 0.00170

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00245

Gnomad4 NFE AF: 0.00337

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00341 Hom.: 0

Bravo AF: 0.00260

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

not provided Benign:1

Likely benign, no assertion criteria provided

clinical testing

Mayo Clinic Laboratories, Mayo Clinic

May 10, 2017

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.0060
Dann	Benign	0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs111271272; hg19: chr11-47264892;