rs12145665

chr1-81562561-A-G

Variant summary

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

The ENST00000473719.5(ADGRL2):n.420-18315A>G variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,168 control chromosomes in the GnomAD database, including 1,612 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 0.12 (1612 hom., cov: 32)
• Consequence: ADGRL2 ENST00000473719.5 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.101

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRL2	NM_001366003.2	c.-309-18315A>G		intron_variant
ADGRL2	NM_001366004.2	c.-309-18315A>G		intron_variant
ADGRL2	NM_001366008.2	c.-247-18315A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRL2	ENST00000473719.5	n.420-18315A>G		intron_variant, non_coding_transcript_variant		1
ADGRL2	ENST00000370721.5	c.-247-18315A>G		intron_variant		5
ADGRL2	ENST00000370723.5	c.-247-18315A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18135 AN: 152050 Hom.: 1604 Cov.: 32

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.0778

Gnomad ASJ AF: 0.0974

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0321

Gnomad FIN AF: 0.0271

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0813

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.119 AC: 18184 AN: 152168 Hom.: 1612 Cov.: 32 AF XY: 0.113 AC XY: 8395 AN XY: 74416

Gnomad4 AFR AF: 0.248

Gnomad4 AMR AF: 0.0777

Gnomad4 ASJ AF: 0.0974

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0315

Gnomad4 FIN AF: 0.0271

Gnomad4 NFE AF: 0.0813

Gnomad4 OTH AF: 0.118

Alfa AF: 0.0888 Hom.: 843

Bravo AF: 0.130

Asia WGS AF: 0.0370 AC: 129 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	1.4
Dann	Benign	0.60

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: rs12145665; hg19: chr1-82028246;