chr2-54115733-A-T

Position:

• chr2-54115733-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_138448.4(ACYP2):​c.35A>T​(p.Tyr12Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ACYP2 NM_138448.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.05

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]

ENSG00000289065 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15602797).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACYP2	NM_001320586.2	c.278-19720A>T		intron_variant		ENST00000607452.6	NP_001307515.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACYP2	ENST00000394666.8	c.35A>T	p.Tyr12Phe	missense_variant	1/4	1		ENSP00000378161.3
ACYP2	ENST00000607452.6	c.278-19720A>T		intron_variant		2	NM_001320586.2	ENSP00000475986.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 11, 2022

The c.35A>T (p.Y12F) alteration is located in exon 1 (coding exon 1) of the ACYP2 gene. This alteration results from a A to T substitution at nucleotide position 35, causing the tyrosine (Y) at amino acid position 12 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.0018	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	19
DANN	Benign	0.92
DEOGEN2	Benign	0.040	T;.;T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.016
FATHMM_MKL	Benign	0.59	D
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.16	T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.8	N;N;N
REVEL	Benign	0.082
Sift	Benign	0.99	T;T;T
Sift4G	Benign	0.94	T;T;T
Polyphen		0.026	.;.;B
Vest4		0.46
MutPred		0.55		.;.;Loss of phosphorylation at Y12 (P = 0.0424);
MVP		0.15
MPC		0.0093
ClinPred		0.96	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.38

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-54342870;