Variant chr1-81907118-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001366006.2(ADGRL2):c.175A>G(p.Ile59Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000323 in 1,614,118 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00032 ( 0 hom. )

Consequence

ADGRL2
NM_001366006.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.40

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.052250504).

BS2

High AC in GnomAd4 at 50 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRL2	NM_001366006.2 linkuse as main transcript	c.175A>G	p.Ile59Val	missense_variant	3/24	ENST00000686636.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRL2	ENST00000686636.1 linkuse as main transcript	c.175A>G	p.Ile59Val	missense_variant	3/24		NM_001366006.2

Frequencies

GnomAD3 genomes

AF:

0.000329

AC:

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000647

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000394

AC:

AN:

251210

Hom.:

AF XY:

0.000390

AC XY:

AN XY:

135756

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000497

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000601

Gnomad NFE exome

AF:

0.000678

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000323

AC:

472

AN:

1461836

Hom.:

Cov.:

AF XY:

0.000359

AC XY:

261

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000268

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00105

Gnomad4 NFE exome

AF:

0.000337

Gnomad4 OTH exome

AF:

0.000546

GnomAD4 genome

AF:

0.000328

AC:

AN:

152282

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.000647

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000562

Hom.:

Bravo

AF:

0.000230

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000436

AC:

EpiCase

AF:

0.000436

EpiControl

AF:

0.000296

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

Aug 26, 2022

The c.175A>G (p.I59V) alteration is located in exon 3 (coding exon 2) of the ADGRL2 gene. This alteration results from a A to G substitution at nucleotide position 175, causing the isoleucine (I) at amino acid position 59 to be replaced by a valine (V). 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

0.25

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

DANN

Uncertain

0.99

Eigen

Benign

-0.0067

Eigen_PC

Benign

0.19

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.86

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

M_CAP

Benign

0.011

MetaRNN

Benign

0.052

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

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.66

D;D;D;D;D;D;D;D;D;D;D;D;D;D

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-0.51

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

REVEL

Benign

0.29

Sift

Benign

0.32

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

Sift4G

Benign

0.85

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

Polyphen

0.15, 0.38, 0.058

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

Vest4

0.33

MVP

0.043

MPC

1.6

ClinPred

0.067

GERP RS

5.1

Varity_R

0.082

gMVP

0.65

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