15-89195345-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_152924.5(ABHD2):c.1200C>T(p.Tyr400=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00664 in 1,614,196 control chromosomes in the GnomAD database, including 67 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0049 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0068 (64 hom.)
• Consequence: ABHD2 NM_152924.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.15

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]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 15-89195345-C-T is Benign according to our data. Variant chr15-89195345-C-T is described in ClinVar as [Benign]. Clinvar id is 777877.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.15 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABHD2	NM_152924.5	c.1200C>T	p.Tyr400=	synonymous_variant	11/11	ENST00000352732.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABHD2	ENST00000352732.10	c.1200C>T	p.Tyr400=	synonymous_variant	11/11	1	NM_152924.5	P1
ABHD2	ENST00000565973.5	c.1200C>T	p.Tyr400=	synonymous_variant	15/15	5		P1

Frequencies

GnomAD3 genomes AF: 0.00493 AC: 750 AN: 152194 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00373

Gnomad ASJ AF: 0.0104

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0114

Gnomad FIN AF: 0.00650

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00666

Gnomad OTH AF: 0.00718

GnomAD3 exomes AF: 0.00616 AC: 1549 AN: 251342 Hom.: 17 AF XY: 0.00687 AC XY: 933 AN XY: 135852

Gnomad AFR exome AF: 0.00141

Gnomad AMR exome AF: 0.00454

Gnomad ASJ exome AF: 0.00893

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0134

Gnomad FIN exome AF: 0.00499

Gnomad NFE exome AF: 0.00641

Gnomad OTH exome AF: 0.00505

GnomAD4 exome AF: 0.00682 AC: 9967 AN: 1461884 Hom.: 64 Cov.: 31 AF XY: 0.00703 AC XY: 5113 AN XY: 727244

Gnomad4 AFR exome AF: 0.00116

Gnomad4 AMR exome AF: 0.00470

Gnomad4 ASJ exome AF: 0.00830

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0144

Gnomad4 FIN exome AF: 0.00502

Gnomad4 NFE exome AF: 0.00675

Gnomad4 OTH exome AF: 0.00705

GnomAD4 genome AF: 0.00491 AC: 748 AN: 152312 Hom.: 3 Cov.: 32 AF XY: 0.00477 AC XY: 355 AN XY: 74490

Gnomad4 AFR AF: 0.00144

Gnomad4 AMR AF: 0.00366

Gnomad4 ASJ AF: 0.0104

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0116

Gnomad4 FIN AF: 0.00650

Gnomad4 NFE AF: 0.00666

Gnomad4 OTH AF: 0.00663

Alfa AF: 0.00665 Hom.: 8

Bravo AF: 0.00462

Asia WGS AF: 0.00491 AC: 17 AN: 3478

EpiCase AF: 0.00791

EpiControl AF: 0.00640

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 23, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
Cadd	Benign	6.8
Dann	Benign	0.56

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: rs147741950; hg19: chr15-89738576;