rs648392

Variant names:

• chr1-81915802-G-A
• rs648392
• NM_001366006.2:c.287+8572G>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.287+8572G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0528 in 152,160 control chromosomes in the GnomAD database, including 597 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 0.053 (597 hom., cov: 32)
• Consequence: ADGRL2 NM_001366006.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.397
• Publications: 1 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.16 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRL2	NM_001366006.2	MANE Select	c.287+8572G>A		intron	N/A	NP_001352935.1	A0A8I5KUX3
	ADGRL2	NM_001366005.2		c.287+8572G>A		intron	N/A	NP_001352934.1	A0A8I5KUX3
	ADGRL2	NM_001350698.2		c.287+8572G>A		intron	N/A	NP_001337627.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRL2	ENST00000686636.1	MANE Select	c.287+8572G>A		intron	N/A	ENSP00000509478.1	A0A8I5KUX3
	ADGRL2	ENST00000370725.5	TSL:5	c.287+8572G>A		intron	N/A	ENSP00000359760.1	O95490-6
	ADGRL2	ENST00000370723.5	TSL:5	c.287+8572G>A		intron	N/A	ENSP00000359758.1	O95490-7

Frequencies

GnomAD3 genomes AF: 0.0528 AC: 8027 AN: 152042 Hom.: 597 Cov.: 32

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0198

Gnomad ASJ AF: 0.0127

Gnomad EAS AF: 0.0346

Gnomad SAS AF: 0.0566

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.00526

Gnomad OTH AF: 0.0435

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

GnomAD4 genome AF: 0.0528 AC: 8041 AN: 152160 Hom.: 597 Cov.: 32 AF XY: 0.0518 AC XY: 3851 AN XY: 74386

African (AFR) AF: 0.163 AC: 6777 AN: 41486

American (AMR) AF: 0.0197 AC: 301 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0127 AC: 44 AN: 3472

East Asian (EAS) AF: 0.0348 AC: 180 AN: 5166

South Asian (SAS) AF: 0.0572 AC: 276 AN: 4822

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10604

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.00526 AC: 358 AN: 68014

Other (OTH) AF: 0.0435 AC: 92 AN: 2116

Alfa AF: 0.0395 Hom.: 72

Bravo AF: 0.0583

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.23
DANN	Benign	0.65
PhyloP100		-0.40
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: rs648392; hg19: chr1-82381486;