Variant 11-47240211-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

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. Variant has been reported in ClinVar as 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 criteria provided, single submitter B:1

Conservation

PhyloP100: 4.73

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 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]. Clinvar id is 788071.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACP2	NM_001610.4 linkuse as main transcript	c.1177T>C	p.Phe393Leu	missense_variant	11/11	ENST00000672073.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACP2	ENST00000672073.1 linkuse as main transcript	c.1177T>C	p.Phe393Leu	missense_variant	11/11		NM_001610.4	P1	P11117-1

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

GnomAD3 exomes

AF:

0.00819

AC:

2057

AN:

251032

Hom.:

AF XY:

0.00841

AC XY:

1141

AN XY:

135678

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 SAS exome

AF:

0.0103

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

Gnomad4 AFR exome

AF:

0.00183

Gnomad4 AMR exome

AF:

0.00257

Gnomad4 ASJ exome

AF:

0.0202

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0108

Gnomad4 FIN exome

AF:

0.0112

Gnomad4 NFE exome

AF:

0.0115

Gnomad4 OTH exome

AF:

0.00960

GnomAD4 genome

AF:

0.00744

AC:

1134

AN:

152348

Hom.:

Cov.:

AF XY:

0.00750

AC XY:

559

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.00202

Gnomad4 AMR

AF:

0.00320

Gnomad4 ASJ

AF:

0.0199

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00745

Gnomad4 FIN

AF:

0.0145

Gnomad4 NFE

AF:

0.0107

Gnomad4 OTH

AF:

0.00567

Alfa

AF:

0.00966

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

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.41

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.50

Cadd

Benign

Dann

Benign

0.95

DEOGEN2

Benign

0.15

T;.;T;T

Eigen

Benign

-0.20

Eigen_PC

Benign

0.046

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.81

T;T;T;T

MetaRNN

Benign

0.0066

T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.74

N;.;.;.

MutationTaster

Benign

0.78

D;D;D;D;N

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-0.11

N;N;N;N

REVEL

Benign

0.056

Sift

Benign

0.69

T;T;T;T

Sift4G

Benign

0.77

T;T;T;T

Polyphen

0.0050

B;B;B;B

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over