Variant 16-84191528-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000315906.10(ADAD2):c.298C>T(p.Pro100Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,394,016 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: 0.000014 ( 0 hom. )

Consequence

ADAD2
ENST00000315906.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.60

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14161703).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAD2	NM_001145400.2 linkuse as main transcript	c.298C>T	p.Pro100Ser	missense_variant	1/10	ENST00000315906.10	NP_001138872.1
ADAD2	NM_139174.4 linkuse as main transcript	c.298C>T	p.Pro100Ser	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.298C>T	p.Pro100Ser	missense_variant	1/10	1	NM_001145400.2	ENSP00000325153	P1	Q8NCV1-1
ADAD2	ENST00000268624.7 linkuse as main transcript	c.298C>T	p.Pro100Ser	missense_variant	1/11	2		ENSP00000268624		Q8NCV1-2
ADAD2	ENST00000567685.1 linkuse as main transcript	c.73C>T	p.Pro25Ser	missense_variant	1/6	3		ENSP00000454950
ADAD2	ENST00000567413.1 linkuse as main transcript	n.338C>T		non_coding_transcript_exon_variant	1/2	4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000143

AC:

AN:

1394016

Hom.:

Cov.:

AF XY:

0.00000727

AC XY:

AN XY:

687732

show subpopulations

Gnomad4 AFR exome

AF:

0.0000317

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:

0.0000167

Gnomad4 OTH exome

AF:

0.0000173

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Nov 12, 2021

The c.298C>T (p.P100S) 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 298, causing the proline (P) at amino acid position 100 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

0.093

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.59

CADD

Benign

9.6

DANN

Benign

0.85

DEOGEN2

Benign

0.0043

.;T

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.57

T;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.78

N;N

REVEL

Benign

0.069

Sift

Benign

0.041

D;T

Sift4G

Benign

0.45

T;T

Polyphen

0.97

D;P

Vest4

0.096

MutPred

0.41

Loss of catalytic residue at P100 (P = 0.0026);Loss of catalytic residue at P100 (P = 0.0026);

MVP

0.36

ClinPred

0.23

GERP RS

3.1

Varity_R

0.033

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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