Variant 15-89195233-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152924.5(ABHD2):c.1088G>A(p.Arg363Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,461,064 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

ABHD2
NM_152924.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.32

Variant links:

Genes affected

ABHD2 (HGNC:18717): (abhydrolase domain containing 2, acylglycerol lipase) This gene encodes a protein containing an alpha/beta hydrolase fold, which is a catalytic domain found in a wide range of enzymes. The encoded protein is an acylglycerol lipase that catalyzes the hydrolysis of endocannabinoid arachidonoylglycerol from the cell membrane. This leads to activation of the sperm calcium channel CatSper, which results in sperm activation. Alternative splicing of this gene results in two transcript variants encoding the same protein. [provided by RefSeq, Jan 2017]

ABHD2 links:

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ACMG classification

Classification made for transcript

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=0.16224205).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABHD2	NM_152924.5 linkuse as main transcript	c.1088G>A	p.Arg363Gln	missense_variant	11/11	ENST00000352732.10	NP_690888.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABHD2	ENST00000352732.10 linkuse as main transcript	c.1088G>A	p.Arg363Gln	missense_variant	11/11	1	NM_152924.5	ENSP00000268129.5		P08910
ABHD2	ENST00000565973.5 linkuse as main transcript	c.1088G>A	p.Arg363Gln	missense_variant	15/15	5		ENSP00000455639.1		P08910

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248646

Hom.:

AF XY:

0.00000744

AC XY:

AN XY:

134460

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000898

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000116

AC:

AN:

1461064

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

726730

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 27, 2022

The c.1088G>A (p.R363Q) alteration is located in exon 15 (coding exon 9) of the ABHD2 gene. This alteration results from a G to A substitution at nucleotide position 1088, causing the arginine (R) at amino acid position 363 to be replaced by a glutamine (Q). 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

0.10

BayesDel_addAF

Benign

-0.060

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.085

T;T

Eigen

Benign

-0.073

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.91

.;D

M_CAP

Benign

0.0092

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.12

N;N

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.94

N;N

REVEL

Benign

0.12

Sift

Benign

0.088

T;T

Sift4G

Benign

0.20

T;T

Polyphen

0.092

B;B

Vest4

0.10

MutPred

0.59

Loss of phosphorylation at S360 (P = 0.1077);Loss of phosphorylation at S360 (P = 0.1077);

MVP

0.58

MPC

0.73

ClinPred

0.33

GERP RS

5.8

Varity_R

0.12

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over