11-47245257-T-G

Variant names:

• chr11-47245257-T-G
• rs2242261
• NM_001610.4:c.639+48A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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

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)

ACMG classification

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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACP2	NM_001610.4	MANE Select	c.639+48A>C		intron	N/A	NP_001601.1	P11117-1
	ACP2	NM_001357016.2		c.639+48A>C		intron	N/A	NP_001343945.1	A0A5F9ZHR7
	ACP2	NM_001302489.2		c.555+48A>C		intron	N/A	NP_001289418.1	E9PQY3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACP2	ENST00000672073.1	MANE Select	c.639+48A>C		intron	N/A	ENSP00000500291.1	P11117-1
	ACP2	ENST00000256997.9	TSL:1	c.639+48A>C		intron	N/A	ENSP00000256997.3	P11117-1
	ACP2	ENST00000672787.1		c.452A>C	p.Gln151Pro	missense splice_region	Exon 5 of 5	ENSP00000500408.1	B7Z6U3

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40592 AN: 151832 Hom.: 6865 Cov.: 32

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

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.: 28 AF XY: 0.190 AC XY: 136067 AN XY: 717184

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

GnomAD4 genome AF: 0.267 AC: 40622 AN: 151950 Hom.: 6870 Cov.: 32 AF XY: 0.277 AC XY: 20576 AN XY: 74264

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: 47 AN: 294

European-Non Finnish (NFE) AF: 0.157 AC: 10656 AN: 67956

Other (OTH) AF: 0.218 AC: 459 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	15
DANN	Benign	0.69
DEOGEN2	Benign	0.0035	T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.36	T
MetaRNN	Benign	0.000012	T
MetaSVM	Benign	-0.97	T
PhyloP100		0.41
PROVEAN	Benign	-0.59	N
REVEL	Benign	0.012
Sift	Benign	0.28	T
Sift4G	Benign	0.13	T
Vest4		0.13
ClinPred		0.0083	T
GERP RS		1.7
Mutation Taster		=87/13	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2242261; hg19: chr11-47266808; COSMIC: COSV57041999; COSMIC: COSV57041999;