11-47240211-A-G

Position:

• chr11-47240211-A-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.73

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 -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]. Clinvar id is 788071.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACP2	NM_001610.4	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	c.1177T>C	p.Phe393Leu	missense_variant	11/11		NM_001610.4	P1

Frequencies

GnomAD3 genomes AF: 0.00745 AC: 1134 AN: 152230 Hom.: 6 Cov.: 32

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.: 14 AF XY: 0.00841 AC XY: 1141 AN XY: 135678

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.: 96 Cov.: 28 AF XY: 0.0107 AC XY: 7791 AN XY: 725066

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.: 6 Cov.: 32 AF XY: 0.00750 AC XY: 559 AN XY: 74500

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.: 13

Bravo AF: 0.00636

TwinsUK AF: 0.0105 AC: 39

ALSPAC AF: 0.0112 AC: 43

ESP6500AA AF: 0.00204 AC: 9

ESP6500EA AF: 0.00989 AC: 85

ExAC AF: 0.00783 AC: 950

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.00943

EpiControl AF: 0.00883

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 06, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	21
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	D
LIST_S2	Benign	0.81	T;T;T;T
MetaRNN	Benign	0.0066	T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.74	N;.;.;.
MutationTaster	Benign	0.78	D;D;D;D;N
PrimateAI	Uncertain	0.69	T
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	T
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

Other links and lift over

dbSNP: rs145420520; hg19: chr11-47261762;