Variant chr19-14743526-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_013447.4(ADGRE2):c.2357G>A(p.Arg786Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0164 in 1,613,930 control chromosomes in the GnomAD database, including 258 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R786W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.010 ( 14 hom., cov: 32)

Exomes 𝑓: 0.017 ( 244 hom. )

Consequence

ADGRE2
NM_013447.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.246

Variant links:

Genes affected

ADGRE2 (HGNC:3337): (adhesion G protein-coupled receptor E2) This gene encodes a member of the class B seven-span transmembrane (TM7) subfamily of G-protein coupled receptors. These proteins are characterized by an extended extracellular region with a variable number of N-terminal epidermal growth factor-like domains coupled to a TM7 domain via a mucin-like spacer domain. The encoded protein is expressed mainly in myeloid cells where it promotes cell-cell adhesion through interaction with chondroitin sulfate chains. This gene is situated in a cluster of related genes on chromosome 19. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2012]

ADGRE2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004303187).

BP6

Variant 19-14743526-C-T is Benign according to our data. Variant chr19-14743526-C-T is described in ClinVar as [Benign]. Clinvar id is 2038299.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0105 (1594/152218) while in subpopulation SAS AF= 0.0199 (96/4818). AF 95% confidence interval is 0.0167. There are 14 homozygotes in gnomad4. There are 720 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1594 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRE2	NM_013447.4 linkuse as main transcript	c.2357G>A	p.Arg786Gln	missense_variant	20/21	ENST00000315576.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRE2	ENST00000315576.8 linkuse as main transcript	c.2357G>A	p.Arg786Gln	missense_variant	20/21	1	NM_013447.4	P3	Q9UHX3-1

Frequencies

GnomAD3 genomes

AF:

0.0105

AC:

1596

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00381

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00635

Gnomad ASJ

AF:

0.00547

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0201

Gnomad FIN

AF:

0.00368

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0171

Gnomad OTH

AF:

0.0119

GnomAD3 exomes

AF:

0.0126

AC:

3179

AN:

251428

Hom.:

AF XY:

0.0138

AC XY:

1876

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.00363

Gnomad AMR exome

AF:

0.00642

Gnomad ASJ exome

AF:

0.00784

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.0214

Gnomad FIN exome

AF:

0.00536

Gnomad NFE exome

AF:

0.0173

Gnomad OTH exome

AF:

0.0122

GnomAD4 exome

AF:

0.0170

AC:

24910

AN:

1461712

Hom.:

244

Cov.:

AF XY:

0.0172

AC XY:

12476

AN XY:

727176

show subpopulations

Gnomad4 AFR exome

AF:

0.00254

Gnomad4 AMR exome

AF:

0.00653

Gnomad4 ASJ exome

AF:

0.00895

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0212

Gnomad4 FIN exome

AF:

0.00550

Gnomad4 NFE exome

AF:

0.0191

Gnomad4 OTH exome

AF:

0.0151

GnomAD4 genome

AF:

0.0105

AC:

1594

AN:

152218

Hom.:

Cov.:

AF XY:

0.00968

AC XY:

720

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.00380

Gnomad4 AMR

AF:

0.00635

Gnomad4 ASJ

AF:

0.00547

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0199

Gnomad4 FIN

AF:

0.00368

Gnomad4 NFE

AF:

0.0170

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.0150

Hom.:

Bravo

AF:

0.0102

TwinsUK

AF:

0.0148

AC:

ALSPAC

AF:

0.0213

AC:

ESP6500AA

AF:

0.00386

AC:

ESP6500EA

AF:

0.0180

AC:

155

ExAC

AF:

0.0137

AC:

1663

Asia WGS

AF:

0.00779

AC:

AN:

3478

EpiCase

AF:

0.0177

EpiControl

AF:

0.0164

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.36

CADD

Benign

7.1

DANN

Benign

0.96

DEOGEN2

Benign

0.053

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

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.78

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

MetaRNN

Benign

0.0043

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

MetaSVM

Benign

-0.98

MutationTaster

Benign

1.0

N;N;N;N;N;N;N

PrimateAI

Benign

0.24

PROVEAN

Uncertain

-2.5

D;.;N;.;.;.;.

REVEL

Benign

0.21

Sift

Benign

0.14

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

Sift4G

Benign

0.27

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

Polyphen

0.054

B;B;.;B;B;P;.

Vest4

0.083

MPC

0.30

ClinPred

0.0044

GERP RS

-3.3

Varity_R

0.067

gMVP

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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