rs11809789

Variant names:

• chr1-81609167-G-A
• rs11809789
• ENST00000370725.5:c.-143+28187G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000370725.5(ADGRL2):​c.-143+28187G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0023 in 152,024 control chromosomes in the GnomAD database, including 3 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 0.0023 (3 hom., cov: 32)
• Consequence: ADGRL2 ENST00000370725.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.123
• Publications: 5 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]

ENSG00000236676 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BS2: High AC in GnomAd4 at 350 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRL2	NM_001366003.2	c.-205+28187G>A		intron_variant	Intron 4 of 27		NP_001352932.1
ADGRL2	NM_001366004.2	c.-205+28187G>A		intron_variant	Intron 4 of 27		NP_001352933.1
ADGRL2	NM_001393349.1	c.-143+28187G>A		intron_variant	Intron 3 of 25		NP_001380278.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRL2	ENST00000370725.5	c.-143+28187G>A		intron_variant	Intron 3 of 25	5		ENSP00000359760.1
ADGRL2	ENST00000370723.5	c.-143+28187G>A		intron_variant	Intron 3 of 24	5		ENSP00000359758.1
ADGRL2	ENST00000370728.5	c.-143+28187G>A		intron_variant	Intron 3 of 24	5		ENSP00000359763.1
ADGRL2	ENST00000370727.5	c.-143+28187G>A		intron_variant	Intron 3 of 24	5		ENSP00000359762.1
ADGRL2	ENST00000370730.5	c.-143+28187G>A		intron_variant	Intron 3 of 23	5		ENSP00000359765.1
ADGRL2	ENST00000370721.5	c.-143+28187G>A		intron_variant	Intron 3 of 24	5		ENSP00000359756.1

Frequencies

GnomAD3 genomes AF: 0.00226 AC: 343 AN: 151904 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00764

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000416

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00287

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

GnomAD4 genome AF: 0.00230 AC: 350 AN: 152024 Hom.: 3 Cov.: 32 AF XY: 0.00235 AC XY: 175 AN XY: 74316

African (AFR) AF: 0.00781 AC: 324 AN: 41468

American (AMR) AF: 0.00118 AC: 18 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4804

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10554

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67992

Other (OTH) AF: 0.00284 AC: 6 AN: 2116

Alfa AF: 0.000610 Hom.: 1

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.73
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism

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: rs11809789; hg19: chr1-82074852;