15-89101707-G-A

Position:

• chr15-89101707-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152924.5(ABHD2):​c.-106-12018G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 152,056 control chromosomes in the GnomAD database, including 18,998 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 0.48 (18998 hom., cov: 32)
• Consequence: ABHD2 NM_152924.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43

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]

LOC124903573 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABHD2	NM_152924.5	c.-106-12018G>A		intron_variant		ENST00000352732.10	NP_690888.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABHD2	ENST00000352732.10	c.-106-12018G>A		intron_variant		1	NM_152924.5	ENSP00000268129.5

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72447 AN: 151938 Hom.: 18956 Cov.: 32

Gnomad AFR AF: 0.694

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.431

Gnomad OTH AF: 0.432

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.477 AC: 72543 AN: 152056 Hom.: 18998 Cov.: 32 AF XY: 0.467 AC XY: 34710 AN XY: 74338

Gnomad4 AFR AF: 0.695

Gnomad4 AMR AF: 0.333

Gnomad4 ASJ AF: 0.310

Gnomad4 EAS AF: 0.188

Gnomad4 SAS AF: 0.384

Gnomad4 FIN AF: 0.390

Gnomad4 NFE AF: 0.431

Gnomad4 OTH AF: 0.433

Alfa AF: 0.454 Hom.: 5424

Bravo AF: 0.482

Asia WGS AF: 0.346 AC: 1203 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.054
DANN	Benign	0.51

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

LitVar

Other links and lift over

dbSNP: rs293381; hg19: chr15-89644938;