1-81932860-C-T

Variant names:

• chr1-81932860-C-T
• rs6681544
• NM_001366006.2:c.288-3868C>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.288-3868C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 151,904 control chromosomes in the GnomAD database, including 7,196 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 0.30 (7196 hom., cov: 32)
• Consequence: ADGRL2 NM_001366006.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.527
• Publications: 0 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 (NFE) allele frequency at 95% confidence interval = 0.352 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.288-3868C>T		intron	N/A	NP_001352935.1	A0A8I5KUX3
	ADGRL2	NM_001366005.2		c.288-3868C>T		intron	N/A	NP_001352934.1	A0A8I5KUX3
	ADGRL2	NM_001350698.2		c.288-3868C>T		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.288-3868C>T		intron	N/A	ENSP00000509478.1	A0A8I5KUX3
	ADGRL2	ENST00000370725.5	TSL:5	c.288-3868C>T		intron	N/A	ENSP00000359760.1	O95490-6
	ADGRL2	ENST00000370723.5	TSL:5	c.288-3868C>T		intron	N/A	ENSP00000359758.1	O95490-7

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44814 AN: 151786 Hom.: 7197 Cov.: 32

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.603

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.317

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

GnomAD4 genome AF: 0.295 AC: 44825 AN: 151904 Hom.: 7196 Cov.: 32 AF XY: 0.292 AC XY: 21711 AN XY: 74228

African (AFR) AF: 0.193 AC: 8002 AN: 41400

American (AMR) AF: 0.256 AC: 3904 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.365 AC: 1267 AN: 3468

East Asian (EAS) AF: 0.162 AC: 837 AN: 5154

South Asian (SAS) AF: 0.293 AC: 1410 AN: 4816

European-Finnish (FIN) AF: 0.370 AC: 3899 AN: 10534

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.356 AC: 24176 AN: 67946

Other (OTH) AF: 0.319 AC: 671 AN: 2104

Alfa AF: 0.307 Hom.: 922

Bravo AF: 0.283

Asia WGS AF: 0.231 AC: 806 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.8
DANN	Benign	0.46
PhyloP100		-0.53
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: rs6681544; hg19: chr1-82398544;