Variant 19-18009974-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000222250.5(ARRDC2):c.784C>T(p.Arg262Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000131 in 1,603,132 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R262Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

ARRDC2
ENST00000222250.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.45

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3293172).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ARRDC2	NM_015683.2 linkuse as main transcript	c.784C>T	p.Arg262Trp	missense_variant	5/8	ENST00000222250.5	NP_056498.1
ARRDC2	NM_001286826.2 linkuse as main transcript	c.784C>T	p.Arg262Trp	missense_variant	5/8		NP_001273755.1
ARRDC2	NM_001025604.3 linkuse as main transcript	c.769C>T	p.Arg257Trp	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.784C>T	p.Arg262Trp	missense_variant	5/8	1	NM_015683.2	ENSP00000222250	P1	Q8TBH0-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152204

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:

0.000578

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:

0.0000426

AC:

AN:

234834

Hom.:

AF XY:

0.0000387

AC XY:

AN XY:

129160

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000395

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000693

Gnomad NFE exome

AF:

0.0000185

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000124

AC:

AN:

1450808

Hom.:

Cov.:

AF XY:

0.0000111

AC XY:

AN XY:

722170

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000231

Gnomad4 NFE exome

AF:

0.0000108

Gnomad4 OTH exome

AF:

0.0000498

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152324

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.0000416

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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, 2023

The c.784C>T (p.R262W) alteration is located in exon 5 (coding exon 5) of the ARRDC2 gene. This alteration results from a C to T substitution at nucleotide position 784, causing the arginine (R) at amino acid position 262 to be replaced by a tryptophan (W). 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

0.16

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.40

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.060

.;.;T

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.97

LIST_S2

Pathogenic

0.99

D;D;D

M_CAP

Benign

0.045

MetaRNN

Benign

0.33

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.0

.;.;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.47

PROVEAN

Pathogenic

-5.3

D;.;D

REVEL

Benign

0.27

Sift

Pathogenic

0.0

D;.;D

Sift4G

Uncertain

0.0030

D;D;D

Polyphen

1.0

D;.;D

Vest4

0.47

MutPred

0.61

.;.;Loss of MoRF binding (P = 0.0567);

MVP

0.77

MPC

1.1

ClinPred

0.84

GERP RS

3.4

Varity_R

0.71

gMVP

0.61

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