Genetic Variant ACP2:c.639+48A>C (chr11-47245257-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001610.4(ACP2):c.639+48A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 1,590,562 control chromosomes in the GnomAD database, including 40,891 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.27 ( 6870 hom., cov: 32)

Exomes 𝑓: 0.19 ( 34021 hom. )

Consequence

ACP2
NM_001610.4 intron

Scores

Splicing: ADA: 0.00009571

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.410

Publications

24 publications found

Variant links:

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]

ACP2 Gene-Disease associations (from GenCC):

lysosomal acid phosphatase deficiency
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.1716715E-5).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACP2	NM_001610.4 link	c.639+48A>C		intron_variant	Intron 6 of 10	ENST00000672073.1	NP_001601.1	P11117-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACP2	ENST00000672073.1 link	c.639+48A>C		intron_variant	Intron 6 of 10		NM_001610.4	ENSP00000500291.1		P11117-1

Frequencies

GnomAD3 genomes

AF:

0.267

AC:

40592

AN:

151832

Hom.:

6865

Cov.:

show subpopulations

Gnomad AFR

AF:

0.414

Gnomad AMI

AF:

0.0811

Gnomad AMR

AF:

0.274

Gnomad ASJ

AF:

0.131

Gnomad EAS

AF:

0.650

Gnomad SAS

AF:

0.235

Gnomad FIN

AF:

0.296

Gnomad MID

AF:

0.165

Gnomad NFE

AF:

0.157

Gnomad OTH

AF:

0.221

GnomAD2 exomes

AF:

0.258

AC:

64848

AN:

251090

AF XY:

0.244

show subpopulations

Gnomad AFR exome

AF:

0.414

Gnomad AMR exome

AF:

0.387

Gnomad ASJ exome

AF:

0.130

Gnomad EAS exome

AF:

0.670

Gnomad FIN exome

AF:

0.282

Gnomad NFE exome

AF:

0.149

Gnomad OTH exome

AF:

0.191

GnomAD4 exome

AF:

0.191

AC:

274279

AN:

1438612

Hom.:

34021

Cov.:

AF XY:

0.190

AC XY:

136067

AN XY:

717184

show subpopulations

African (AFR)

AF:

0.419

AC:

13829

AN:

33042

American (AMR)

AF:

0.372

AC:

16632

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.130

AC:

3374

AN:

26008

East Asian (EAS)

AF:

0.654

AC:

25905

AN:

39588

South Asian (SAS)

AF:

0.235

AC:

20148

AN:

85882

European-Finnish (FIN)

AF:

0.266

AC:

14126

AN:

53128

Middle Eastern (MID)

AF:

0.165

AC:

943

AN:

5722

European-Non Finnish (NFE)

AF:

0.153

AC:

167306

AN:

1090950

Other (OTH)

AF:

0.202

AC:

12016

AN:

59590

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

10763

21526

32288

43051

53814

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6438

12876

19314

25752

32190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.267

AC:

40622

AN:

151950

Hom.:

6870

Cov.:

AF XY:

0.277

AC XY:

20576

AN XY:

74264

show subpopulations

African (AFR)

AF:

0.413

AC:

17131

AN:

41432

American (AMR)

AF:

0.274

AC:

4188

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.131

AC:

456

AN:

3468

East Asian (EAS)

AF:

0.651

AC:

3355

AN:

5150

South Asian (SAS)

AF:

0.235

AC:

1134

AN:

4816

European-Finnish (FIN)

AF:

0.296

AC:

3122

AN:

10556

Middle Eastern (MID)

AF:

0.160

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.157

AC:

10656

AN:

67956

Other (OTH)

AF:

0.218

AC:

459

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1383

2766

4148

5531

6914

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

406

812

1218

1624

2030

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.190

Hom.:

8434

Bravo

AF:

0.275

TwinsUK

AF:

0.151

AC:

560

ALSPAC

AF:

0.154

AC:

593

ESP6500AA

AF:

0.396

AC:

1743

ESP6500EA

AF:

0.149

AC:

1282

ExAC

AF:

0.249

AC:

30268

Asia WGS

AF:

0.349

AC:

1210

AN:

3478

EpiCase

AF:

0.142

EpiControl

AF:

0.134

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.69

DEOGEN2

Benign

0.0035

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.24

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.36

MetaRNN

Benign

0.000012

MetaSVM

Benign

-0.97

PhyloP100

0.41

PROVEAN

Benign

-0.59

REVEL

Benign

0.012

Sift

Benign

0.28

Sift4G

Benign

0.13

Vest4

0.13

ClinPred

0.0083

GERP RS

1.7

Mutation Taster

=87/13

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000096

dbscSNV1_RF

Benign

0.018

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over