dbSNP rs11988: ACP2:c.*407C>T (chr11-47239709-G-A) – 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.*407C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 166,912 control chromosomes in the GnomAD database, including 7,834 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 0.28 ( 6951 hom., cov: 32)

Exomes 𝑓: 0.32 ( 883 hom. )

Consequence

ACP2
NM_001610.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.374

Publications

23 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 (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACP2	NM_001610.4 link	c.*407C>T		3_prime_UTR_variant	Exon 11 of 11	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.*407C>T		3_prime_UTR_variant	Exon 11 of 11		NM_001610.4	ENSP00000500291.1		P11117-1

Frequencies

GnomAD3 genomes

AF:

0.276

AC:

41925

AN:

151956

Hom.:

6954

Cov.:

show subpopulations

Gnomad AFR

AF:

0.118

Gnomad AMI

AF:

0.362

Gnomad AMR

AF:

0.251

Gnomad ASJ

AF:

0.380

Gnomad EAS

AF:

0.0216

Gnomad SAS

AF:

0.250

Gnomad FIN

AF:

0.310

Gnomad MID

AF:

0.342

Gnomad NFE

AF:

0.386

Gnomad OTH

AF:

0.313

GnomAD4 exome

AF:

0.320

AC:

4753

AN:

14838

Hom.:

883

Cov.:

AF XY:

0.327

AC XY:

2455

AN XY:

7504

show subpopulations

African (AFR)

AF:

0.120

AC:

AN:

510

American (AMR)

AF:

0.171

AC:

184

AN:

1074

Ashkenazi Jewish (ASJ)

AF:

0.347

AC:

186

AN:

536

East Asian (EAS)

AF:

0.0164

AC:

AN:

852

South Asian (SAS)

AF:

0.241

AC:

146

AN:

606

European-Finnish (FIN)

AF:

0.335

AC:

166

AN:

496

Middle Eastern (MID)

AF:

0.406

AC:

AN:

European-Non Finnish (NFE)

AF:

0.379

AC:

3705

AN:

9782

Other (OTH)

AF:

0.289

AC:

265

AN:

918

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

158

316

473

631

789

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

136

170

<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:

0.276

AC:

41922

AN:

152074

Hom.:

6951

Cov.:

AF XY:

0.269

AC XY:

20021

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.118

AC:

4884

AN:

41520

American (AMR)

AF:

0.250

AC:

3828

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.380

AC:

1320

AN:

3472

East Asian (EAS)

AF:

0.0218

AC:

113

AN:

5180

South Asian (SAS)

AF:

0.250

AC:

1202

AN:

4814

European-Finnish (FIN)

AF:

0.310

AC:

3261

AN:

10536

Middle Eastern (MID)

AF:

0.347

AC:

102

AN:

294

European-Non Finnish (NFE)

AF:

0.386

AC:

26229

AN:

67950

Other (OTH)

AF:

0.309

AC:

654

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1462

2923

4385

5846

7308

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

428

856

1284

1712

2140

<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:

0.349

Hom.:

42467

Bravo

AF:

0.263

Asia WGS

AF:

0.140

AC:

487

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

6.5

(source)

DANN

Benign

0.68

PhyloP100

0.37

Mutation Taster

=100/0

polymorphism (auto)

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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