rs2296697

chr1-81971535-G-Achr1-81971535-G-T

Variant summary

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

The NM_001366006.2(ADGRL2):c.2955-317G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 151,950 control chromosomes in the GnomAD database, including 11,831 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 0.38 (11831 hom., cov: 32)
• Consequence: ADGRL2 NM_001366006.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0520

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.668 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRL2	NM_001366006.2	c.2955-317G>A		intron_variant		ENST00000686636.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRL2	ENST00000686636.1	c.2955-317G>A		intron_variant			NM_001366006.2

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58367 AN: 151832 Hom.: 11811 Cov.: 32

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.446

Gnomad EAS AF: 0.687

Gnomad SAS AF: 0.512

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.395

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

GnomAD4 genome AF: 0.385 AC: 58439 AN: 151950 Hom.: 11831 Cov.: 32 AF XY: 0.383 AC XY: 28442 AN XY: 74270

Gnomad4 AFR AF: 0.438

Gnomad4 AMR AF: 0.418

Gnomad4 ASJ AF: 0.446

Gnomad4 EAS AF: 0.686

Gnomad4 SAS AF: 0.512

Gnomad4 FIN AF: 0.208

Gnomad4 NFE AF: 0.338

Gnomad4 OTH AF: 0.396

Alfa AF: 0.362 Hom.: 4817

Bravo AF: 0.403

Asia WGS AF: 0.582 AC: 2022 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	2.5
Dann	Benign	0.44

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: rs2296697; hg19: chr1-82437219;