rs12145665

Variant names:

• chr1-81562561-A-G
• rs12145665
• ENST00000370725.5:c.-247-18315A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001366003.2(ADGRL2):​c.-309-18315A>G variant causes a intron 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 NM_001366003.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.101
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366003.2. 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
	ADGRL2	NM_001366003.2		c.-309-18315A>G		intron	N/A	NP_001352932.1
	ADGRL2	NM_001366004.2		c.-309-18315A>G		intron	N/A	NP_001352933.1
	ADGRL2	NM_001393349.1		c.-247-18315A>G		intron	N/A	NP_001380278.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRL2	ENST00000370725.5	TSL:5	c.-247-18315A>G		intron	N/A	ENSP00000359760.1	O95490-6
	ADGRL2	ENST00000370723.5	TSL:5	c.-247-18315A>G		intron	N/A	ENSP00000359758.1	O95490-7
	ADGRL2	ENST00000370728.5	TSL:5	c.-247-18315A>G		intron	N/A	ENSP00000359763.1	O95490-1

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

African (AFR) AF: 0.248 AC: 10285 AN: 41490

American (AMR) AF: 0.0777 AC: 1187 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0974 AC: 338 AN: 3472

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5190

South Asian (SAS) AF: 0.0315 AC: 152 AN: 4826

European-Finnish (FIN) AF: 0.0271 AC: 287 AN: 10604

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.0813 AC: 5529 AN: 67986

Other (OTH) AF: 0.118 AC: 248 AN: 2110

Alfa AF: 0.0945 Hom.: 1286

Bravo AF: 0.130

Asia WGS AF: 0.0370 AC: 129 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.4
DANN	Benign	0.60
PhyloP100		-0.10
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12145665; hg19: chr1-82028246;