Variant 19-18009662-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 NM_015683.2(ARRDC2):c.560C>T(p.Ser187Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000739 in 1,610,918 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 (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000075 ( 0 hom. )

Consequence

ARRDC2
NM_015683.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.88

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:

ARRDC2 (HGNC:):

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=0.37279943).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARRDC2	NM_015683.2 linkuse as main transcript	c.560C>T	p.Ser187Leu	missense_variant	4/8	ENST00000222250.5	NP_056498.1	Q8TBH0-1A0A024R7K1
ARRDC2	NM_001286826.2 linkuse as main transcript	c.560C>T	p.Ser187Leu	missense_variant	4/8		NP_001273755.1	Q8TBH0
ARRDC2	NM_001025604.3 linkuse as main transcript	c.545C>T	p.Ser182Leu	missense_variant	4/8		NP_001020775.1	Q8TBH0-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARRDC2	ENST00000222250.5 linkuse as main transcript	c.560C>T	p.Ser187Leu	missense_variant	4/8	1	NM_015683.2	ENSP00000222250.3		Q8TBH0-1

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152162

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000479

AC:

AN:

250568

Hom.:

AF XY:

0.0000517

AC XY:

AN XY:

135442

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000747

AC:

109

AN:

1458756

Hom.:

Cov.:

AF XY:

0.0000717

AC XY:

AN XY:

725088

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000937

Gnomad4 OTH exome

AF:

0.0000664

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152162

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000987

Hom.:

Bravo

AF:

0.0000453

ExAC

AF:

0.0000576

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000178

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

Feb 15, 2023

The c.560C>T (p.S187L) alteration is located in exon 4 (coding exon 4) of the ARRDC2 gene. This alteration results from a C to T substitution at nucleotide position 560, causing the serine (S) at amino acid position 187 to be replaced by a leucine (L). 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

0.12

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.017

.;.;T

Eigen

Benign

0.15

Eigen_PC

Benign

0.075

FATHMM_MKL

Uncertain

0.80

LIST_S2

Pathogenic

1.0

D;D;D

M_CAP

Benign

0.020

MetaRNN

Benign

0.37

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

.;.;L

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-3.2

D;.;D

REVEL

Benign

0.14

Sift

Uncertain

0.0010

D;.;D

Sift4G

Uncertain

0.0080

D;D;D

Polyphen

0.99

D;.;D

Vest4

0.63

MVP

0.40

MPC

1.0

ClinPred

0.50

GERP RS

4.9

Varity_R

0.50

gMVP

0.58

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