rs147741950

Variant names:

• chr15-89195345-C-A
• rs147741950
• NM_152924.5:c.1200C>A

Your query was ambiguous. Multiple possible variants found:

• chr15-89195345-C-A
• chr15-89195345-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_152924.5(ABHD2):​c.1200C>A​(p.Tyr400*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Y400Y) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ABHD2 NM_152924.5 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152924.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABHD2	NM_152924.5	MANE Select	c.1200C>A	p.Tyr400*	stop_gained	Exon 11 of 11	NP_690888.1	A0A024RC89
	ABHD2	NM_001416412.1		c.1200C>A	p.Tyr400*	stop_gained	Exon 13 of 13	NP_001403341.1	A0A024RC89
	ABHD2	NM_001416413.1		c.1200C>A	p.Tyr400*	stop_gained	Exon 14 of 14	NP_001403342.1	A0A024RC89

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABHD2	ENST00000352732.10	TSL:1 MANE Select	c.1200C>A	p.Tyr400*	stop_gained	Exon 11 of 11	ENSP00000268129.5	P08910
	ABHD2	ENST00000565973.5	TSL:5	c.1200C>A	p.Tyr400*	stop_gained	Exon 15 of 15	ENSP00000455639.1	P08910
	ABHD2	ENST00000864961.1		c.1200C>A	p.Tyr400*	stop_gained	Exon 10 of 10	ENSP00000535020.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461886 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727244

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.44	D
BayesDel_noAF	Pathogenic	0.39
CADD	Pathogenic	33
DANN	Uncertain	0.99
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.21	N
PhyloP100		-1.2
Vest4		0.38
GERP RS		-4.1

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

Other links and lift over

dbSNP: rs147741950; hg19: chr15-89738576;