NM_001145400.2:c.86C>A

Variant summary

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

The NM_001145400.2(ADAD2):​c.86C>A​(p.Pro29His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000209 in 1,436,406 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P29R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 35)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ADAD2
NM_001145400.2 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.119
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]

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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=0.05910641).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ADAD2NM_001145400.2 linkc.86C>A p.Pro29His missense_variant Exon 1 of 10 ENST00000315906.10 NP_001138872.1 Q8NCV1-1
ADAD2NM_139174.4 linkc.86C>A p.Pro29His missense_variant Exon 1 of 11 NP_631913.3 Q8NCV1-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ADAD2ENST00000315906.10 linkc.86C>A p.Pro29His missense_variant Exon 1 of 10 1 NM_001145400.2 ENSP00000325153.6 Q8NCV1-1
ADAD2ENST00000268624.7 linkc.86C>A p.Pro29His missense_variant Exon 1 of 11 2 ENSP00000268624.3 Q8NCV1-2
ADAD2ENST00000567413.1 linkn.126C>A non_coding_transcript_exon_variant Exon 1 of 2 4
ADAD2ENST00000567685.1 linkc.-143C>A upstream_gene_variant 3 ENSP00000454950.1 H3BNP6

Frequencies

GnomAD3 genomes
Cov.:
35
GnomAD4 exome
AF:
0.00000209
AC:
3
AN:
1436406
Hom.:
0
Cov.:
89
AF XY:
0.00000140
AC XY:
1
AN XY:
711756
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:
0.00000273
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.099
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.72
CADD
Benign
9.4
DANN
Benign
0.83
DEOGEN2
Benign
0.0021
.;T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.060
N
LIST_S2
Benign
0.38
T;T
M_CAP
Benign
0.0052
T
MetaRNN
Benign
0.059
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N;N
PrimateAI
Benign
0.43
T
PROVEAN
Benign
-1.3
N;N
REVEL
Benign
0.0080
Sift
Benign
0.087
T;T
Sift4G
Benign
0.35
T;T
Polyphen
0.0020
B;B
Vest4
0.19
MutPred
0.27
Gain of helix (P = 6e-04);Gain of helix (P = 6e-04);
MVP
0.14
ClinPred
0.026
T
GERP RS
1.2
Varity_R
0.055
gMVP
0.19

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.

Other links and lift over

hg19: chr16-84224922; API