chr2-54135454-T-A

Position:

• chr2-54135454-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001320586.2(ACYP2):​c.279T>A​(p.Ser93Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00252 in 1,607,950 control chromosomes in the GnomAD database, including 92 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.014 (55 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (37 hom.)
• Consequence: ACYP2 NM_001320586.2 missense, splice_region
• Scores: Splicing: ADA: 0.0002627
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.47

Genes affected

ACYP2 (HGNC:180): (acylphosphatase 2) Acylphosphatase can hydrolyze the phosphoenzyme intermediate of different membrane pumps, particularly the Ca2+/Mg2+-ATPase from sarcoplasmic reticulum of skeletal muscle. Two isoenzymes have been isolated, called muscle acylphosphatase and erythrocyte acylphosphatase on the basis of their tissue localization. This gene encodes the muscle-type isoform (MT). An increase of the MT isoform is associated with muscle differentiation. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0065383017).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0136 (2068/152228) while in subpopulation AFR AF= 0.0476 (1976/41538). AF 95% confidence interval is 0.0458. There are 55 homozygotes in gnomad4. There are 965 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 55 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACYP2	NM_001320586.2	c.279T>A	p.Ser93Arg	missense_variant, splice_region_variant	5/7	ENST00000607452.6	NP_001307515.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACYP2	ENST00000607452.6	c.279T>A	p.Ser93Arg	missense_variant, splice_region_variant	5/7	2	NM_001320586.2	ENSP00000475986

Frequencies

GnomAD3 genomes AF: 0.0136 AC: 2064 AN: 152110 Hom.: 55 Cov.: 32

Gnomad AFR AF: 0.0476

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00400

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00908

GnomAD3 exomes AF: 0.00342 AC: 846 AN: 247234 Hom.: 14 AF XY: 0.00263 AC XY: 352 AN XY: 133674

Gnomad AFR exome AF: 0.0479

Gnomad AMR exome AF: 0.00153

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000677

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000106

Gnomad OTH exome AF: 0.00150

GnomAD4 exome AF: 0.00136 AC: 1985 AN: 1455722 Hom.: 37 Cov.: 29 AF XY: 0.00117 AC XY: 851 AN XY: 724280

Gnomad4 AFR exome AF: 0.0485

Gnomad4 AMR exome AF: 0.00195

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000353

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000848

Gnomad4 OTH exome AF: 0.00304

GnomAD4 genome AF: 0.0136 AC: 2068 AN: 152228 Hom.: 55 Cov.: 32 AF XY: 0.0130 AC XY: 965 AN XY: 74440

Gnomad4 AFR AF: 0.0476

Gnomad4 AMR AF: 0.00399

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.00899

Alfa AF: 0.00195 Hom.: 2

Bravo AF: 0.0153

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0540 AC: 238

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00462 AC: 561

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	19
DANN	Benign	0.58
DEOGEN2	Benign	0.089	T
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.24	T
MetaRNN	Benign	0.0065	T
MutationTaster	Benign	1.0	D;D;D
Sift4G	Uncertain	0.0080	D
Vest4		0.30
MVP		0.63
GERP RS		0.19
gMVP		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00026
dbscSNV1_RF	Benign	0.048
SpliceAI score (max)		0.030		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: rs13405053; hg19: chr2-54362591;