1-81932860-C-T

Position:

• chr1-81932860-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRL2	NM_001366006.2	c.288-3868C>T		intron_variant		ENST00000686636.1	NP_001352935.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRL2	ENST00000686636.1	c.288-3868C>T		intron_variant			NM_001366006.2	ENSP00000509478

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

Gnomad4 AFR AF: 0.193

Gnomad4 AMR AF: 0.256

Gnomad4 ASJ AF: 0.365

Gnomad4 EAS AF: 0.162

Gnomad4 SAS AF: 0.293

Gnomad4 FIN AF: 0.370

Gnomad4 NFE AF: 0.356

Gnomad4 OTH AF: 0.319

Alfa AF: 0.312 Hom.: 907

Bravo AF: 0.283

Asia WGS AF: 0.231 AC: 806 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.8
DANN	Benign	0.46

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: rs6681544; hg19: chr1-82398544;