Variant 10-1233838-G-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_018702.4(ADARB2):c.1369C>A(p.Arg457Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000855 in 1,613,410 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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. R457C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000077 ( 1 hom. )

Consequence

ADARB2
NM_018702.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.76

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28819844).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADARB2	NM_018702.4 linkuse as main transcript	c.1369C>A	p.Arg457Ser	missense_variant	6/10	ENST00000381312.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADARB2	ENST00000381312.6 linkuse as main transcript	c.1369C>A	p.Arg457Ser	missense_variant	6/10	1	NM_018702.4	P1	Q9NS39-1
LINC00200	ENST00000655745.1 linkuse as main transcript	n.265-54635G>T		intron_variant, non_coding_transcript_variant
ADARB2	ENST00000469464.1 linkuse as main transcript	n.153C>A		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes

AF:

0.000178

AC:

AN:

152052

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.0000678

AC:

AN:

250614

Hom.:

AF XY:

0.0000738

AC XY:

AN XY:

135470

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000459

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000766

AC:

112

AN:

1461240

Hom.:

Cov.:

AF XY:

0.000100

AC XY:

AN XY:

726904

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000557

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000369

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.000171

AC:

AN:

152170

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.0000386

Hom.:

Bravo

AF:

0.000253

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000906

AC:

EpiCase

AF:

0.000164

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

May 05, 2023

The c.1369C>A (p.R457S) alteration is located in exon 6 (coding exon 6) of the ADARB2 gene. This alteration results from a C to A substitution at nucleotide position 1369, causing the arginine (R) at amino acid position 457 to be replaced by a serine (S). 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

0.19

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.18

Cadd

Benign

Dann

Benign

0.97

DEOGEN2

Benign

0.084

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.083

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.82

M_CAP

Benign

0.057

MetaRNN

Benign

0.29

MetaSVM

Uncertain

0.029

MutationAssessor

Benign

1.3

MutationTaster

Benign

0.92

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.5

REVEL

Benign

0.25

Sift

Benign

0.53

Sift4G

Benign

0.74

Polyphen

0.018

Vest4

0.51

MVP

0.51

MPC

0.91

ClinPred

0.092

GERP RS

5.5

Varity_R

0.27

gMVP

0.43

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