Variant chr16-84191474-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001145400.2(ADAD2):c.244C>T(p.Arg82Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000178 in 1,537,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

ADAD2
NM_001145400.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.63

Variant links:

Genes affected

ADAD2 (HGNC:30714): (adenosine deaminase domain containing 2) Predicted to enable double-stranded RNA adenosine deaminase activity; double-stranded RNA binding activity; and tRNA-specific adenosine deaminase activity. Predicted to be involved in RNA processing and adenosine to inosine editing. Predicted to be active in cytoplasm and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

ADAD2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.033415884).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAD2	NM_001145400.2 link	c.244C>T	p.Arg82Trp	missense_variant	1/10	ENST00000315906.10	NP_001138872.1	Q8NCV1-1
ADAD2	NM_139174.4 link	c.244C>T	p.Arg82Trp	missense_variant	1/11		NP_631913.3	Q8NCV1-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ADAD2	ENST00000315906.10 link	c.244C>T	p.Arg82Trp	missense_variant	1/10	1	NM_001145400.2	ENSP00000325153.6	Q8NCV1-1
ADAD2	ENST00000268624.7 link	c.244C>T	p.Arg82Trp	missense_variant	1/11	2		ENSP00000268624.3	Q8NCV1-2
ADAD2	ENST00000567685.1 link	c.16C>T	p.Arg6Trp	missense_variant	1/6	3		ENSP00000454950.1	H3BNP6
ADAD2	ENST00000567413.1 link	n.284C>T		non_coding_transcript_exon_variant	1/2	4

Frequencies

GnomAD3 genomes

AF:

0.000105

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000814

AC:

AN:

135214

Hom.:

AF XY:

0.0000410

AC XY:

AN XY:

73082

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000222

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000185

AC:

257

AN:

1385554

Hom.:

Cov.:

AF XY:

0.000190

AC XY:

130

AN XY:

683356

show subpopulations

Gnomad4 AFR exome

AF:

0.0000319

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000127

Gnomad4 FIN exome

AF:

0.0000240

Gnomad4 NFE exome

AF:

0.000230

Gnomad4 OTH exome

AF:

0.000104

GnomAD4 genome

AF:

0.000105

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74366

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:

0.000235

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000286

Hom.:

Bravo

AF:

0.000113

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000138

AC:

ExAC

AF:

0.0000145

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Jul 06, 2021

The c.244C>T (p.R82W) alteration is located in exon 1 (coding exon 1) of the ADAD2 gene. This alteration results from a C to T substitution at nucleotide position 244, causing the arginine (R) at amino acid position 82 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

0.10

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.70

CADD

Benign

5.5

DANN

Benign

0.93

DEOGEN2

Benign

0.0053

.;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0069

LIST_S2

Benign

0.52

T;T

M_CAP

Benign

0.0079

MetaRNN

Benign

0.033

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.20

N;N

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.021

Sift

Benign

0.13

T;T

Sift4G

Benign

0.098

T;T

Polyphen

0.0

B;B

Vest4

0.14

MVP

0.067

ClinPred

0.041

GERP RS

-2.9

Varity_R

0.040

gMVP

0.21

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