Variant chr16-84191489-T-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000315906.10(ADAD2):c.259T>G(p.Leu87Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000144 in 1,388,058 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: not found (cov: 34)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ADAD2
ENST00000315906.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -4.11

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:

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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=0.039983213).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAD2	NM_001145400.2 linkuse as main transcript	c.259T>G	p.Leu87Val	missense_variant	1/10	ENST00000315906.10	NP_001138872.1
ADAD2	NM_139174.4 linkuse as main transcript	c.259T>G	p.Leu87Val	missense_variant	1/11		NP_631913.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAD2	ENST00000315906.10 linkuse as main transcript	c.259T>G	p.Leu87Val	missense_variant	1/10	1	NM_001145400.2	ENSP00000325153	P1	Q8NCV1-1
ADAD2	ENST00000268624.7 linkuse as main transcript	c.259T>G	p.Leu87Val	missense_variant	1/11	2		ENSP00000268624		Q8NCV1-2
ADAD2	ENST00000567685.1 linkuse as main transcript	c.34T>G	p.Leu12Val	missense_variant	1/6	3		ENSP00000454950
ADAD2	ENST00000567413.1 linkuse as main transcript	n.299T>G		non_coding_transcript_exon_variant	1/2	4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000144

AC:

AN:

1388058

Hom.:

Cov.:

AF XY:

0.00000292

AC XY:

AN XY:

684714

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000186

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 08, 2024

The c.259T>G (p.L87V) alteration is located in exon 1 (coding exon 1) of the ADAD2 gene. This alteration results from a T to G substitution at nucleotide position 259, causing the leucine (L) at amino acid position 87 to be replaced by a valine (V). 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

0.066

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.0030

DANN

Benign

0.59

DEOGEN2

Benign

0.0019

.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0041

LIST_S2

Benign

0.40

T;T

M_CAP

Benign

0.0043

MetaRNN

Benign

0.040

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.49

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.28

N;N

REVEL

Benign

0.011

Sift

Benign

0.47

T;T

Sift4G

Benign

0.59

T;T

Polyphen

0.0090

B;B

Vest4

0.057

MutPred

0.34

Gain of catalytic residue at L87 (P = 0.0152);Gain of catalytic residue at L87 (P = 0.0152);

MVP

0.076

ClinPred

0.27

GERP RS

-3.2

Varity_R

0.032

gMVP

0.070

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over