rs145420520

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001610.4(ACP2):c.1177T>C(p.Phe393Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0104 in 1,609,010 control chromosomes in the GnomAD database, including 102 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0074 ( 6 hom., cov: 32)

Exomes 𝑓: 0.011 ( 96 hom. )

Consequence

ACP2
NM_001610.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 4.73

Publications

10 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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0066221356).

BP6

Variant 11-47240211-A-G is Benign according to our data. Variant chr11-47240211-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 788071.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 6 Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001610.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ACP2	NM_001610.4	MANE Select	c.1177T>C	p.Phe393Leu	missense	Exon 11 of 11	NP_001601.1	P11117-1
ACP2	NM_001357016.2		c.1177T>C	p.Phe393Leu	missense	Exon 11 of 11	NP_001343945.1	A0A5F9ZHR7
ACP2	NM_001302489.2		c.1093T>C	p.Phe365Leu	missense	Exon 11 of 11	NP_001289418.1	E9PQY3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ACP2	ENST00000672073.1	MANE Select	c.1177T>C	p.Phe393Leu	missense	Exon 11 of 11	ENSP00000500291.1	P11117-1
ACP2	ENST00000256997.9	TSL:1	c.1177T>C	p.Phe393Leu	missense	Exon 11 of 11	ENSP00000256997.3	P11117-1
ACP2	ENST00000672636.2		c.1177T>C	p.Phe393Leu	missense	Exon 11 of 11	ENSP00000500571.2	A0A5F9ZHR7

Frequencies

GnomAD3 genomes

AF:

0.00745

AC:

1134

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00203

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00321

Gnomad ASJ

AF:

0.0199

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00744

Gnomad FIN

AF:

0.0145

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0107

Gnomad OTH

AF:

0.00573

GnomAD2 exomes

AF:

0.00819

AC:

2057

AN:

251032

AF XY:

0.00841

show subpopulations

Gnomad AFR exome

AF:

0.00210

Gnomad AMR exome

AF:

0.00237

Gnomad ASJ exome

AF:

0.0196

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0116

Gnomad NFE exome

AF:

0.0101

Gnomad OTH exome

AF:

0.00588

GnomAD4 exome

AF:

0.0107

AC:

15652

AN:

1456662

Hom.:

Cov.:

AF XY:

0.0107

AC XY:

7791

AN XY:

725066

show subpopulations

African (AFR)

AF:

0.00183

AC:

AN:

33372

American (AMR)

AF:

0.00257

AC:

115

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0202

AC:

526

AN:

26096

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39666

South Asian (SAS)

AF:

0.0108

AC:

932

AN:

86154

European-Finnish (FIN)

AF:

0.0112

AC:

600

AN:

53410

Middle Eastern (MID)

AF:

0.0104

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.0115

AC:

12779

AN:

1107300

Other (OTH)

AF:

0.00960

AC:

578

AN:

60192

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

751

1502

2254

3005

3756

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

510

1020

1530

2040

2550

<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:

0.00744

AC:

1134

AN:

152348

Hom.:

Cov.:

AF XY:

0.00750

AC XY:

559

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.00202

AC:

AN:

41590

American (AMR)

AF:

0.00320

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0199

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5182

South Asian (SAS)

AF:

0.00745

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0145

AC:

154

AN:

10624

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0107

AC:

728

AN:

68020

Other (OTH)

AF:

0.00567

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

118

178

237

296

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

100

<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:

0.00944

Hom.:

Bravo

AF:

0.00636

TwinsUK

AF:

0.0105

AC:

ALSPAC

AF:

0.0112

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.00989

AC:

ExAC

AF:

0.00783

AC:

950

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.00943

EpiControl

AF:

0.00883

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.41

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.15

Eigen

Benign

-0.20

Eigen_PC

Benign

0.046

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.81

MetaRNN

Benign

0.0066

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.74

PhyloP100

4.7

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-0.11

REVEL

Benign

0.056

Sift

Benign

0.69

Sift4G

Benign

0.77

Polyphen

0.0050

Vest4

0.18

MutPred

0.47

Loss of catalytic residue at F393 (P = 0.1428)

MVP

0.25

MPC

0.43

ClinPred

0.032

GERP RS

5.7

Varity_R

0.087

gMVP

0.60

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over