chr1-81837028-T-C

Position:

chr1-81837028-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001366006.2(ADGRL2):c.44T>C(p.Ile15Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000188 in 1,593,438 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ADGRL2
NM_001366006.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.83

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13046992).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRL2	NM_001366006.2 link	c.44T>C	p.Ile15Thr	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.44T>C	p.Ile15Thr	missense_variant	2/24		NM_001366006.2	ENSP00000509478.1	A0A8I5KUX3
ADGRL2	ENST00000370725.5 link	c.44T>C	p.Ile15Thr	missense_variant	5/26	5		ENSP00000359760.1	O95490-6
ADGRL2	ENST00000370723.5 link	c.44T>C	p.Ile15Thr	missense_variant	5/25	5		ENSP00000359758.1	O95490-7
ADGRL2	ENST00000370728.5 link	c.44T>C	p.Ile15Thr	missense_variant	5/25	5		ENSP00000359763.1	O95490-1
ADGRL2	ENST00000370727.5 link	c.44T>C	p.Ile15Thr	missense_variant	5/25	5		ENSP00000359762.1	B1ALU3
ADGRL2	ENST00000370730.5 link	c.44T>C	p.Ile15Thr	missense_variant	5/24	5		ENSP00000359765.1	O95490-5
ADGRL2	ENST00000370721.5 link	c.44T>C	p.Ile15Thr	missense_variant	5/25	5		ENSP00000359756.1	B1ALU1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152086

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:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000861

AC:

AN:

232308

Hom.:

AF XY:

0.0000159

AC XY:

AN XY:

125902

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000120

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000139

AC:

AN:

1441352

Hom.:

Cov.:

AF XY:

0.00000279

AC XY:

AN XY:

716760

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000262

Gnomad4 SAS exome

AF:

0.0000121

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152086

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

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

Sep 20, 2023

The c.44T>C (p.I15T) alteration is located in exon 2 (coding exon 1) of the ADGRL2 gene. This alteration results from a T to C substitution at nucleotide position 44, causing the isoleucine (I) at amino acid position 15 to be replaced by a threonine (T). 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

0.085

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

DANN

Benign

0.91

DEOGEN2

Benign

0.023

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

Eigen

Benign

-0.13

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.92

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

M_CAP

Benign

0.012

MetaRNN

Benign

0.13

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

MetaSVM

Benign

-0.99

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-0.64

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

REVEL

Benign

0.23

Sift

Uncertain

0.0050

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

Sift4G

Benign

0.23

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

Polyphen

0.0

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

Vest4

0.61

MutPred

0.49

Loss of stability (P = 0.0352);Loss of stability (P = 0.0352);Loss of stability (P = 0.0352);Loss of stability (P = 0.0352);Loss of stability (P = 0.0352);Loss of stability (P = 0.0352);Loss of stability (P = 0.0352);Loss of stability (P = 0.0352);Loss of stability (P = 0.0352);Loss of stability (P = 0.0352);Loss of stability (P = 0.0352);Loss of stability (P = 0.0352);

MVP

0.043

MPC

0.89

ClinPred

0.21

GERP RS

5.4

Varity_R

0.12

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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