Variant 19-14397738-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000242786.6(ADGRE5):c.706C>T(p.Arg236Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000458 in 1,419,528 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R236H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000062 ( 0 hom., cov: 18)

Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

ADGRE5
ENST00000242786.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0310

Variant links:

Genes affected

ADGRE5 (HGNC:1711): (adhesion G protein-coupled receptor E5) This gene encodes a member of the EGF-TM7 subfamily of adhesion G protein-coupled receptors, which mediate cell-cell interactions. These proteins are cleaved by self-catalytic proteolysis into a large extracellular subunit and seven-span transmembrane subunit, which associate at the cell surface as a receptor complex. The encoded protein may play a role in cell adhesion as well as leukocyte recruitment, activation and migration, and contains multiple extracellular EGF-like repeats which mediate binding to chondroitin sulfate and the cell surface complement regulatory protein CD55. Expression of this gene may play a role in the progression of several types of cancer. Alternatively spliced transcript variants encoding multiple isoforms with 3 to 5 EGF-like repeats have been observed for this gene. This gene is found in a cluster with other EGF-TM7 genes on the short arm of chromosome 19. [provided by RefSeq, Jun 2011]

ADGRE5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ADGRE5	NM_078481.4 linkuse as main transcript	c.706C>T	p.Arg236Cys	missense_variant	7/20	ENST00000242786.6	NP_510966.1
ADGRE5	NM_001025160.3 linkuse as main transcript	c.559C>T	p.Arg187Cys	missense_variant	6/19		NP_001020331.1
ADGRE5	NM_001784.6 linkuse as main transcript	c.427C>T	p.Arg143Cys	missense_variant	5/18		NP_001775.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRE5	ENST00000242786.6 linkuse as main transcript	c.706C>T	p.Arg236Cys	missense_variant	7/20	1	NM_078481.4	ENSP00000242786	P1	P48960-1

Frequencies

GnomAD3 genomes

AF:

0.0000616

AC:

AN:

129784

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000150

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000251

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000161

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000726

AC:

AN:

206614

Hom.:

AF XY:

0.0000528

AC XY:

AN XY:

113628

show subpopulations

Gnomad AFR exome

AF:

0.000169

Gnomad AMR exome

AF:

0.000138

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000369

Gnomad FIN exome

AF:

0.0000550

Gnomad NFE exome

AF:

0.0000659

Gnomad OTH exome

AF:

0.000192

GnomAD4 exome

AF:

0.0000442

AC:

AN:

1289744

Hom.:

Cov.:

AF XY:

0.0000417

AC XY:

AN XY:

646984

show subpopulations

Gnomad4 AFR exome

AF:

0.0000677

Gnomad4 AMR exome

AF:

0.000164

Gnomad4 ASJ exome

AF:

0.0000402

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000368

Gnomad4 FIN exome

AF:

0.0000384

Gnomad4 NFE exome

AF:

0.0000426

Gnomad4 OTH exome

AF:

0.0000184

GnomAD4 genome

AF:

0.0000616

AC:

AN:

129784

Hom.:

Cov.:

AF XY:

0.0000648

AC XY:

AN XY:

61732

show subpopulations

Gnomad4 AFR

AF:

0.000150

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000251

Gnomad4 NFE

AF:

0.0000161

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000673

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

Mar 01, 2024

The c.706C>T (p.R236C) alteration is located in exon 7 (coding exon 7) of the ADGRE5 gene. This alteration results from a C to T substitution at nucleotide position 706, causing the arginine (R) at amino acid position 236 to be replaced by a cysteine (C). 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

0.22

BayesDel_addAF

Benign

-0.080

BayesDel_noAF

Benign

-0.090

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.61

.;D;.;.

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.59

T;T;T;D

M_CAP

Uncertain

0.11

MetaRNN

Uncertain

0.48

T;T;T;T

MetaSVM

Uncertain

0.14

MutationTaster

Benign

0.52

D;D;D

PrimateAI

Benign

0.21

PROVEAN

Pathogenic

-4.6

D;.;D;D

REVEL

Uncertain

0.39

Sift

Benign

0.13

T;.;D;T

Sift4G

Benign

0.21

T;T;T;T

Vest4

0.21

MVP

0.67

MPC

2.5

ClinPred

0.85

GERP RS

0.21

gMVP

0.70

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