Variant 1-81837010-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001366006.2(ADGRL2):c.26G>A(p.Arg9Gln) variant causes a missense change. The variant allele was found at a frequency of 0.002 in 1,593,248 control chromosomes in the GnomAD database, including 5 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0021 ( 5 hom. )

Consequence

ADGRL2
NM_001366006.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.14

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006865263).

BP6

Variant 1-81837010-G-A is Benign according to our data. Variant chr1-81837010-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2638898.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 231 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRL2	NM_001366006.2 link	c.26G>A	p.Arg9Gln	missense_variant	2/24	ENST00000686636.1	NP_001352935.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ADGRL2	ENST00000686636.1 link	c.26G>A	p.Arg9Gln	missense_variant	2/24		NM_001366006.2	ENSP00000509478.1	A0A8I5KUX3
ADGRL2	ENST00000370725.5 link	c.26G>A	p.Arg9Gln	missense_variant	5/26	5		ENSP00000359760.1	O95490-6
ADGRL2	ENST00000370723.5 link	c.26G>A	p.Arg9Gln	missense_variant	5/25	5		ENSP00000359758.1	O95490-7
ADGRL2	ENST00000370728.5 link	c.26G>A	p.Arg9Gln	missense_variant	5/25	5		ENSP00000359763.1	O95490-1
ADGRL2	ENST00000370727.5 link	c.26G>A	p.Arg9Gln	missense_variant	5/25	5		ENSP00000359762.1	B1ALU3
ADGRL2	ENST00000370730.5 link	c.26G>A	p.Arg9Gln	missense_variant	5/24	5		ENSP00000359765.1	O95490-5
ADGRL2	ENST00000370721.5 link	c.26G>A	p.Arg9Gln	missense_variant	5/25	5		ENSP00000359756.1	B1ALU1

Frequencies

GnomAD3 genomes

AF:

0.00152

AC:

231

AN:

152014

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00276

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00227

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00107

AC:

249

AN:

233110

Hom.:

AF XY:

0.00102

AC XY:

129

AN XY:

126376

show subpopulations

Gnomad AFR exome

AF:

0.000673

Gnomad AMR exome

AF:

0.00111

Gnomad ASJ exome

AF:

0.00144

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000187

Gnomad NFE exome

AF:

0.00164

Gnomad OTH exome

AF:

0.00201

GnomAD4 exome

AF:

0.00205

AC:

2957

AN:

1441116

Hom.:

Cov.:

AF XY:

0.00196

AC XY:

1404

AN XY:

716742

show subpopulations

Gnomad4 AFR exome

AF:

0.000374

Gnomad4 AMR exome

AF:

0.00110

Gnomad4 ASJ exome

AF:

0.00128

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000169

Gnomad4 NFE exome

AF:

0.00245

Gnomad4 OTH exome

AF:

0.00264

GnomAD4 genome

AF:

0.00152

AC:

231

AN:

152132

Hom.:

Cov.:

AF XY:

0.00145

AC XY:

108

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.000481

Gnomad4 AMR

AF:

0.00275

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00227

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00166

Hom.:

Bravo

AF:

0.00158

TwinsUK

AF:

0.00431

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00233

AC:

ExAC

AF:

0.000890

AC:

108

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2022

ADGRL2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.011

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

Eigen

Benign

-0.13

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.77

LIST_S2

Uncertain

0.96

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

M_CAP

Benign

0.0056

MetaRNN

Benign

0.0069

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

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.66

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

REVEL

Benign

0.13

Sift

Benign

0.095

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

Sift4G

Benign

0.59

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

Polyphen

0.0

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

Vest4

0.11

MVP

0.11

MPC

0.81

ClinPred

0.017

GERP RS

5.4

Varity_R

0.053

gMVP

0.37

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