rs754054

Variant names:

• chr1-81833886-A-G
• rs754054
• NM_001366006.2:c.-100-2999A>G

Variant summary

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

The NM_001366006.2(ADGRL2):​c.-100-2999A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 152,000 control chromosomes in the GnomAD database, including 8,987 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 0.33 (8987 hom., cov: 32)
• Consequence: ADGRL2 NM_001366006.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.20
• 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=-0.5).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366006.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRL2	NM_001366006.2	MANE Select	c.-100-2999A>G		intron	N/A	NP_001352935.1
	ADGRL2	NM_001366005.2		c.-100-2999A>G		intron	N/A	NP_001352934.1
	ADGRL2	NM_001350698.2		c.-100-2999A>G		intron	N/A	NP_001337627.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRL2	ENST00000686636.1	MANE Select	c.-100-2999A>G		intron	N/A	ENSP00000509478.1
	ADGRL2	ENST00000370725.5	TSL:5	c.-100-2999A>G		intron	N/A	ENSP00000359760.1
	ADGRL2	ENST00000370723.5	TSL:5	c.-100-2999A>G		intron	N/A	ENSP00000359758.1

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50741 AN: 151882 Hom.: 8977 Cov.: 32

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.480

Gnomad EAS AF: 0.00347

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.369

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

GnomAD4 genome AF: 0.334 AC: 50781 AN: 152000 Hom.: 8987 Cov.: 32 AF XY: 0.331 AC XY: 24564 AN XY: 74298

African (AFR) AF: 0.388 AC: 16055 AN: 41432

American (AMR) AF: 0.269 AC: 4110 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.480 AC: 1664 AN: 3466

East Asian (EAS) AF: 0.00367 AC: 19 AN: 5176

South Asian (SAS) AF: 0.227 AC: 1094 AN: 4818

European-Finnish (FIN) AF: 0.343 AC: 3614 AN: 10546

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.337 AC: 22879 AN: 67976

Other (OTH) AF: 0.364 AC: 769 AN: 2112

Alfa AF: 0.339 Hom.: 26302

Bravo AF: 0.330

Asia WGS AF: 0.134 AC: 469 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	14
DANN	Benign	0.67
PhyloP100		1.2
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: rs754054; hg19: chr1-82299571; COSMIC: COSV54659255;