rs12072054

Positions:

• chr1-81777398-A-G

Variant summary

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

The ENST00000359929.7(ADGRL2):​c.-101+15546A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 152,186 control chromosomes in the GnomAD database, including 3,425 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 0.20 (3425 hom., cov: 33)
• Consequence: ADGRL2 ENST00000359929.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.416

Genes affected

ADGRL2 (HGNC:18582): (adhesion G protein-coupled receptor L2) This gene encodes a member of the latrophilin subfamily of G-protein coupled receptors. The encoded protein participates in the regulation of exocytosis. The proprotein is thought to be further cleaved within a cysteine-rich G-protein-coupled receptor proteolysis site into two chains that are non-covalently bound at the cell membrane. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRL2	NM_001297704.3	c.-101+15546A>G		intron_variant
ADGRL2	NM_001366003.2	c.-101+15546A>G		intron_variant
ADGRL2	NM_001366004.2	c.-101+15546A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRL2	ENST00000359929.7	c.-101+15546A>G		intron_variant		1
ADGRL2	ENST00000370721.5	c.-101+15546A>G		intron_variant		5
ADGRL2	ENST00000370723.5	c.-101+15546A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30639 AN: 152068 Hom.: 3424 Cov.: 33

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.0785

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.170

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

GnomAD4 genome AF: 0.202 AC: 30672 AN: 152186 Hom.: 3425 Cov.: 33 AF XY: 0.203 AC XY: 15094 AN XY: 74400

Gnomad4 AFR AF: 0.288

Gnomad4 AMR AF: 0.204

Gnomad4 ASJ AF: 0.140

Gnomad4 EAS AF: 0.0783

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.185

Gnomad4 NFE AF: 0.169

Gnomad4 OTH AF: 0.170

Alfa AF: 0.167 Hom.: 3591

Bravo AF: 0.203

Asia WGS AF: 0.130 AC: 450 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.3
DANN	Benign	0.50

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: rs12072054; hg19: chr1-82243083;