Variant chr19-14743421-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_013447.4(ADGRE2):c.2462C>T(p.Thr821Met) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00865 in 1,613,330 control chromosomes in the GnomAD database, including 72 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. T821T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0062 ( 6 hom., cov: 31)

Exomes 𝑓: 0.0089 ( 66 hom. )

Consequence

ADGRE2
NM_013447.4 missense, splice_region

Scores

Splicing: ADA: 0.0005739

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.770

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0040538013).

BP6

Variant 19-14743421-G-A is Benign according to our data. Variant chr19-14743421-G-A is described in ClinVar as [Benign]. Clinvar id is 2042980.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 948 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRE2	NM_013447.4 linkuse as main transcript	c.2462C>T	p.Thr821Met	missense_variant, splice_region_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.2462C>T	p.Thr821Met	missense_variant, splice_region_variant	20/21	1	NM_013447.4	P3	Q9UHX3-1

Frequencies

GnomAD3 genomes

AF:

0.00623

AC:

948

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00193

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.00557

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00456

Gnomad FIN

AF:

0.00716

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00979

Gnomad OTH

AF:

0.00528

GnomAD3 exomes

AF:

0.00631

AC:

1585

AN:

251266

Hom.:

AF XY:

0.00637

AC XY:

865

AN XY:

135766

show subpopulations

Gnomad AFR exome

AF:

0.00185

Gnomad AMR exome

AF:

0.00249

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.000217

Gnomad SAS exome

AF:

0.00526

Gnomad FIN exome

AF:

0.00827

Gnomad NFE exome

AF:

0.00952

Gnomad OTH exome

AF:

0.00701

GnomAD4 exome

AF:

0.00890

AC:

13001

AN:

1461070

Hom.:

Cov.:

AF XY:

0.00892

AC XY:

6483

AN XY:

726924

show subpopulations

Gnomad4 AFR exome

AF:

0.00170

Gnomad4 AMR exome

AF:

0.00282

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.00564

Gnomad4 FIN exome

AF:

0.00906

Gnomad4 NFE exome

AF:

0.0102

Gnomad4 OTH exome

AF:

0.00757

GnomAD4 genome

AF:

0.00623

AC:

948

AN:

152260

Hom.:

Cov.:

AF XY:

0.00583

AC XY:

434

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.00193

Gnomad4 AMR

AF:

0.00556

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00456

Gnomad4 FIN

AF:

0.00716

Gnomad4 NFE

AF:

0.00979

Gnomad4 OTH

AF:

0.00523

Alfa

AF:

0.00846

Hom.:

Bravo

AF:

0.00566

TwinsUK

AF:

0.00728

AC:

ALSPAC

AF:

0.0122

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.0106

AC:

ExAC

AF:

0.00669

AC:

812

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.00911

EpiControl

AF:

0.00842

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

0.073

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.38

CADD

Benign

6.5

DANN

Benign

0.79

DEOGEN2

Benign

0.0082

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

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0039

LIST_S2

Benign

0.52

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

MetaRNN

Benign

0.0039

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

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

D;N;N;N;N;N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.88

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

REVEL

Benign

0.13

Sift

Benign

0.19

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

Sift4G

Benign

0.22

T;T;T;T;T;T;D

Polyphen

0.12

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

Vest4

0.11

MVP

0.048

MPC

0.27

ClinPred

0.99

GERP RS

-9.0

Varity_R

0.017

gMVP

0.10

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00057

dbscSNV1_RF

Benign

0.086

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