Variant 1-81943620-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001366006.2(ADGRL2):c.1061G>A(p.Arg354Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000409 in 1,613,500 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000038 ( 1 hom. )

Consequence

ADGRL2
NM_001366006.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.83

Variant links:

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]

ADGRL2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07301366).

BS2

High AC in GnomAd4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRL2	NM_001366006.2 link	c.1061G>A	p.Arg354Gln	missense_variant	6/24	ENST00000686636.1	NP_001352935.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ADGRL2	ENST00000686636.1 link	c.1061G>A	p.Arg354Gln	missense_variant	6/24		NM_001366006.2	ENSP00000509478.1	A0A8I5KUX3
ADGRL2	ENST00000370725.5 link	c.1049G>A	p.Arg350Gln	missense_variant	8/26	5		ENSP00000359760.1	O95490-6
ADGRL2	ENST00000370723.5 link	c.1049G>A	p.Arg350Gln	missense_variant	8/25	5		ENSP00000359758.1	O95490-7
ADGRL2	ENST00000370728.5 link	c.1049G>A	p.Arg350Gln	missense_variant	8/25	5		ENSP00000359763.1	O95490-1
ADGRL2	ENST00000370727.5 link	c.1049G>A	p.Arg350Gln	missense_variant	8/25	5		ENSP00000359762.1	B1ALU3
ADGRL2	ENST00000370730.5 link	c.1049G>A	p.Arg350Gln	missense_variant	8/24	5		ENSP00000359765.1	O95490-5
ADGRL2	ENST00000370721.5 link	c.1061G>A	p.Arg354Gln	missense_variant	9/25	5		ENSP00000359756.1	B1ALU1

Frequencies

GnomAD3 genomes

AF:

0.0000724

AC:

AN:

151936

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000718

AC:

AN:

250818

Hom.:

AF XY:

0.000103

AC XY:

AN XY:

135536

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000376

AC:

AN:

1461564

Hom.:

Cov.:

AF XY:

0.0000481

AC XY:

AN XY:

727086

show subpopulations

Gnomad4 AFR exome

AF:

0.000389

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000383

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000724

AC:

AN:

151936

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74200

show subpopulations

Gnomad4 AFR

AF:

0.000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000988

Hom.:

Bravo

AF:

0.000106

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000906

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 31, 2024

The c.1049G>A (p.R350Q) alteration is located in exon 5 (coding exon 4) of the ADGRL2 gene. This alteration results from a G to A substitution at nucleotide position 1049, causing the arginine (R) at amino acid position 350 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.38

.;T;.;.;D;.;.;.;.;.;T;D

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.014

FATHMM_MKL

Uncertain

0.91

LIST_S2

Pathogenic

0.98

D;.;D;D;.;D;.;D;D;D;D;D

M_CAP

Benign

0.022

MetaRNN

Benign

0.073

T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.51

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-1.3

N;N;N;N;N;N;N;N;N;N;.;N

REVEL

Benign

0.25

Sift

Benign

0.21

T;T;T;T;T;T;T;T;T;T;.;T

Sift4G

Benign

0.21

T;T;T;T;T;T;T;T;T;T;T;T

Polyphen

0.14, 0.040

.;.;.;.;.;.;B;B;B;B;.;.

Vest4

0.31

MVP

0.44

MPC

0.81

ClinPred

0.048

GERP RS

4.6

Varity_R

0.11

gMVP

0.31

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over