rs371363

Variant names:

• chr1-81883669-C-T
• rs371363
• NM_001366006.2:c.74-23348C>T

Variant summary

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

The NM_001366006.2(ADGRL2):​c.74-23348C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,102 control chromosomes in the GnomAD database, including 1,608 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 0.14 (1608 hom., cov: 32)
• Consequence: ADGRL2 NM_001366006.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.848
• 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRL2	NM_001366006.2	c.74-23348C>T		intron_variant	Intron 2 of 23	ENST00000686636.1	NP_001352935.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRL2	ENST00000686636.1	c.74-23348C>T		intron_variant	Intron 2 of 23		NM_001366006.2	ENSP00000509478.1
ADGRL2	ENST00000370725.5	c.74-23348C>T		intron_variant	Intron 5 of 25	5		ENSP00000359760.1
ADGRL2	ENST00000370723.5	c.74-23348C>T		intron_variant	Intron 5 of 24	5		ENSP00000359758.1
ADGRL2	ENST00000370728.5	c.74-23348C>T		intron_variant	Intron 5 of 24	5		ENSP00000359763.1
ADGRL2	ENST00000370727.5	c.74-23348C>T		intron_variant	Intron 5 of 24	5		ENSP00000359762.1
ADGRL2	ENST00000370730.5	c.74-23348C>T		intron_variant	Intron 5 of 23	5		ENSP00000359765.1
ADGRL2	ENST00000370721.5	c.74-23348C>T		intron_variant	Intron 5 of 24	5		ENSP00000359756.1

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20823 AN: 151982 Hom.: 1601 Cov.: 32

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.0827

Gnomad EAS AF: 0.0423

Gnomad SAS AF: 0.0483

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.0701

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.124

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

GnomAD4 genome AF: 0.137 AC: 20850 AN: 152102 Hom.: 1608 Cov.: 32 AF XY: 0.137 AC XY: 10152 AN XY: 74340

African (AFR) AF: 0.176 AC: 7290 AN: 41490

American (AMR) AF: 0.213 AC: 3248 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0827 AC: 287 AN: 3470

East Asian (EAS) AF: 0.0422 AC: 218 AN: 5164

South Asian (SAS) AF: 0.0477 AC: 230 AN: 4822

European-Finnish (FIN) AF: 0.108 AC: 1145 AN: 10578

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.119 AC: 8107 AN: 67982

Other (OTH) AF: 0.122 AC: 257 AN: 2112

Alfa AF: 0.130 Hom.: 173

Bravo AF: 0.148

Asia WGS AF: 0.0680 AC: 235 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.83
DANN	Benign	0.60
PhyloP100		-0.85
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: rs371363; hg19: chr1-82349354;