Variant 10-1184875-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_018702.4(ADARB2):c.2029C>T(p.Arg677Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000158 in 1,613,248 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. R677Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

ADARB2
NM_018702.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.91

Variant links:

Genes affected

ADARB2 (HGNC:227): (adenosine deaminase RNA specific B2 (inactive)) This gene encodes a member of the double-stranded RNA adenosine deaminase family of RNA-editing enzymes and may play a regulatory role in RNA editing. [provided by RefSeq, Jul 2008]

ADARB2 links:

LINC00200 (HGNC:30974): (long intergenic non-protein coding RNA 200)

LINC00200 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	UniProt
ADARB2	NM_018702.4 linkuse as main transcript	c.2029C>T	p.Arg677Trp	missense_variant	9/10	ENST00000381312.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADARB2	ENST00000381312.6 linkuse as main transcript	c.2029C>T	p.Arg677Trp	missense_variant	9/10	1	NM_018702.4	P1	Q9NS39-1
LINC00200	ENST00000655745.1 linkuse as main transcript	n.264+24238G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000847

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000273

AC:

AN:

248746

Hom.:

AF XY:

0.000319

AC XY:

AN XY:

134814

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.000458

Gnomad FIN exome

AF:

0.000886

Gnomad NFE exome

AF:

0.000286

Gnomad OTH exome

AF:

0.000330

GnomAD4 exome

AF:

0.000159

AC:

232

AN:

1461008

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

137

AN XY:

726798

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000348

Gnomad4 FIN exome

AF:

0.00104

Gnomad4 NFE exome

AF:

0.000114

Gnomad4 OTH exome

AF:

0.000215

GnomAD4 genome

AF:

0.000151

AC:

AN:

152240

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000847

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.000479

Alfa

AF:

0.000152

Hom.:

Bravo

AF:

0.000155

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000280

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

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

Sep 29, 2023

The c.2029C>T (p.R677W) alteration is located in exon 9 (coding exon 9) of the ADARB2 gene. This alteration results from a C to T substitution at nucleotide position 2029, causing the arginine (R) at amino acid position 677 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

0.12

BayesDel_addAF

Benign

-0.075

BayesDel_noAF

Uncertain

-0.010

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Uncertain

0.71

D;.;.

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.26

LIST_S2

Uncertain

0.92

D;D;D

M_CAP

Pathogenic

0.42

MetaRNN

Uncertain

0.71

D;D;D

MetaSVM

Uncertain

0.59

MutationAssessor

Uncertain

2.8

M;.;.

MutationTaster

Benign

0.93

N;N;N

PrimateAI

Benign

0.27

PROVEAN

Pathogenic

-5.3

D;D;D

REVEL

Uncertain

0.45

Sift

Uncertain

0.0090

D;D;D

Sift4G

Uncertain

0.011

D;D;D

Polyphen

1.0

D;.;D

Vest4

0.61

MVP

0.71

MPC

0.82

ClinPred

0.35

GERP RS

1.9

Varity_R

0.30

gMVP

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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