rs10874241

Positions:

• chr1-81422920-G-A

Variant summary

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

The ENST00000473719.5(ADGRL2):​n.351-22101G>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.942 in 152,274 control chromosomes in the GnomAD database, including 67,967 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 0.94 (67967 hom., cov: 33)
• Consequence: ADGRL2 ENST00000473719.5 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.220

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.985 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRL2	NM_001366003.2	c.-378-22101G>A		intron_variant
ADGRL2	NM_001366004.2	c.-379+8569G>A		intron_variant
ADGRL2	NM_001366008.2	c.-316-22101G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRL2	ENST00000473719.5	n.351-22101G>A		intron_variant, non_coding_transcript_variant		1
ADGRL2	ENST00000370721.5	c.-301-22116G>A		intron_variant		5
ADGRL2	ENST00000370723.5	c.-301-22116G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.942 AC: 143360 AN: 152156 Hom.: 67923 Cov.: 33

Gnomad AFR AF: 0.826

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.972

Gnomad ASJ AF: 0.995

Gnomad EAS AF: 0.955

Gnomad SAS AF: 0.967

Gnomad FIN AF: 0.993

Gnomad MID AF: 0.972

Gnomad NFE AF: 0.991

Gnomad OTH AF: 0.960

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

GnomAD4 genome AF: 0.942 AC: 143458 AN: 152274 Hom.: 67967 Cov.: 33 AF XY: 0.944 AC XY: 70257 AN XY: 74460

Gnomad4 AFR AF: 0.826

Gnomad4 AMR AF: 0.972

Gnomad4 ASJ AF: 0.995

Gnomad4 EAS AF: 0.955

Gnomad4 SAS AF: 0.966

Gnomad4 FIN AF: 0.993

Gnomad4 NFE AF: 0.991

Gnomad4 OTH AF: 0.961

Alfa AF: 0.982 Hom.: 90746

Bravo AF: 0.935

Asia WGS AF: 0.960 AC: 3339 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.3
DANN	Benign	0.68

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: rs10874241; hg19: chr1-81888605; COSMIC: COSV65860587; COSMIC: COSV65860587;