1-81971535-G-A

Variant names:

• chr1-81971535-G-A
• rs2296697
• NM_001366006.2:c.2955-317G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.668 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.2955-317G>A		intron	N/A	NP_001352935.1
	ADGRL2	NM_001366005.2		c.2955-317G>A		intron	N/A	NP_001352934.1
	ADGRL2	NM_001350698.2		c.2955-317G>A		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.2955-317G>A		intron	N/A	ENSP00000509478.1
	ADGRL2	ENST00000370725.5	TSL:5	c.2943-317G>A		intron	N/A	ENSP00000359760.1
	ADGRL2	ENST00000370723.5	TSL:5	c.2904-317G>A		intron	N/A	ENSP00000359758.1

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

African (AFR) AF: 0.438 AC: 18156 AN: 41436

American (AMR) AF: 0.418 AC: 6375 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.446 AC: 1548 AN: 3468

East Asian (EAS) AF: 0.686 AC: 3545 AN: 5164

South Asian (SAS) AF: 0.512 AC: 2466 AN: 4818

European-Finnish (FIN) AF: 0.208 AC: 2203 AN: 10566

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.338 AC: 22953 AN: 67918

Other (OTH) AF: 0.396 AC: 835 AN: 2110

Alfa AF: 0.362 Hom.: 5394

Bravo AF: 0.403

Asia WGS AF: 0.582 AC: 2022 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.5
DANN	Benign	0.44
PhyloP100		-0.052
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: rs2296697; hg19: chr1-82437219;