Variant chr1-81950298-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001366006.2(ADGRL2):c.1320A>T(p.Gly440=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0219 in 1,614,064 control chromosomes in the GnomAD database, including 565 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.016 ( 45 hom., cov: 32)

Exomes 𝑓: 0.022 ( 520 hom. )

Consequence

ADGRL2
NM_001366006.2 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.44

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 1-81950298-A-T is Benign according to our data. Variant chr1-81950298-A-T is described in ClinVar as [Benign]. Clinvar id is 3055525.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=2.44 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.054 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRL2	NM_001366006.2 linkuse as main transcript	c.1320A>T	p.Gly440=	synonymous_variant	7/24	ENST00000686636.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRL2	ENST00000686636.1 linkuse as main transcript	c.1320A>T	p.Gly440=	synonymous_variant	7/24		NM_001366006.2

Frequencies

GnomAD3 genomes

AF:

0.0164

AC:

2499

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00371

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.0104

Gnomad ASJ

AF:

0.0651

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0590

Gnomad FIN

AF:

0.00970

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0224

Gnomad OTH

AF:

0.0172

GnomAD3 exomes

AF:

0.0210

AC:

5280

AN:

250986

Hom.:

111

AF XY:

0.0229

AC XY:

3106

AN XY:

135650

show subpopulations

Gnomad AFR exome

AF:

0.00382

Gnomad AMR exome

AF:

0.00842

Gnomad ASJ exome

AF:

0.0578

Gnomad EAS exome

AF:

0.000436

Gnomad SAS exome

AF:

0.0497

Gnomad FIN exome

AF:

0.0112

Gnomad NFE exome

AF:

0.0217

Gnomad OTH exome

AF:

0.0180

GnomAD4 exome

AF:

0.0224

AC:

32789

AN:

1461774

Hom.:

520

Cov.:

AF XY:

0.0233

AC XY:

16943

AN XY:

727174

show subpopulations

Gnomad4 AFR exome

AF:

0.00284

Gnomad4 AMR exome

AF:

0.00890

Gnomad4 ASJ exome

AF:

0.0584

Gnomad4 EAS exome

AF:

0.000277

Gnomad4 SAS exome

AF:

0.0518

Gnomad4 FIN exome

AF:

0.0126

Gnomad4 NFE exome

AF:

0.0218

Gnomad4 OTH exome

AF:

0.0218

GnomAD4 genome

AF:

0.0164

AC:

2505

AN:

152290

Hom.:

Cov.:

AF XY:

0.0159

AC XY:

1187

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00370

Gnomad4 AMR

AF:

0.0104

Gnomad4 ASJ

AF:

0.0651

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.0597

Gnomad4 FIN

AF:

0.00970

Gnomad4 NFE

AF:

0.0224

Gnomad4 OTH

AF:

0.0184

Alfa

AF:

0.0238

Hom.:

Bravo

AF:

0.0144

Asia WGS

AF:

0.0230

AC:

AN:

3478

EpiCase

AF:

0.0199

EpiControl

AF:

0.0169

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

ADGRL2-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 13, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

7.0

DANN

Benign

0.66

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