Variant 19-18009975-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000222250.5(ARRDC2):c.785G>A(p.Arg262Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000923 in 1,603,204 control chromosomes in the GnomAD database, including 8 homozygotes. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R262W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0032 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00068 ( 7 hom. )

Consequence

ARRDC2
ENST00000222250.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.79

Variant links:

Genes affected

ARRDC2 (HGNC:25225): (arrestin domain containing 2) Predicted to be involved in protein transport. Located in cytoplasmic vesicle and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ARRDC2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0122329).

BS2

High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ARRDC2	NM_015683.2 linkuse as main transcript	c.785G>A	p.Arg262Gln	missense_variant	5/8	ENST00000222250.5	NP_056498.1
ARRDC2	NM_001286826.2 linkuse as main transcript	c.785G>A	p.Arg262Gln	missense_variant	5/8		NP_001273755.1
ARRDC2	NM_001025604.3 linkuse as main transcript	c.770G>A	p.Arg257Gln	missense_variant	5/8		NP_001020775.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARRDC2	ENST00000222250.5 linkuse as main transcript	c.785G>A	p.Arg262Gln	missense_variant	5/8	1	NM_015683.2	ENSP00000222250	P1	Q8TBH0-1

Frequencies

GnomAD3 genomes

AF:

0.00322

AC:

490

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0103

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00212

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000957

AC:

225

AN:

235094

Hom.:

AF XY:

0.000781

AC XY:

101

AN XY:

129246

show subpopulations

Gnomad AFR exome

AF:

0.0102

Gnomad AMR exome

AF:

0.000734

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000678

Gnomad SAS exome

AF:

0.0000656

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000269

Gnomad OTH exome

AF:

0.00119

GnomAD4 exome

AF:

0.000683

AC:

991

AN:

1450890

Hom.:

Cov.:

AF XY:

0.000645

AC XY:

466

AN XY:

722224

show subpopulations

Gnomad4 AFR exome

AF:

0.0116

Gnomad4 AMR exome

AF:

0.000967

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00746

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000175

Gnomad4 OTH exome

AF:

0.000929

GnomAD4 genome

AF:

0.00321

AC:

489

AN:

152314

Hom.:

Cov.:

AF XY:

0.00328

AC XY:

244

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.0102

Gnomad4 AMR

AF:

0.00196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00212

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000654

Hom.:

Bravo

AF:

0.00358

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00826

AC:

ESP6500EA

AF:

0.000118

AC:

ExAC

AF:

0.000957

AC:

115

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000296

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Sep 21, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.00082

.;.;T

Eigen

Benign

0.031

Eigen_PC

Benign

0.026

FATHMM_MKL

Benign

0.64

LIST_S2

Uncertain

0.89

D;D;D

MetaRNN

Benign

0.012

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

.;.;L

MutationTaster

Benign

0.99

D;D

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.1

N;.;N

REVEL

Benign

0.13

Sift

Uncertain

0.0060

D;.;D

Sift4G

Uncertain

0.038

D;T;T

Polyphen

0.98

D;.;D

Vest4

0.23

MVP

0.60

MPC

0.50

ClinPred

0.022

GERP RS

0.73

Varity_R

0.17

gMVP

0.32

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