16-84191316-C-A

Variant names:

• chr16-84191316-C-A
• rs759599115
• NM_001145400.2:c.86C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_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. 16/22 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.119
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05910641).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145400.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAD2	NM_001145400.2	MANE Select	c.86C>A	p.Pro29His	missense	Exon 1 of 10	NP_001138872.1	Q8NCV1-1
	ADAD2	NM_139174.4		c.86C>A	p.Pro29His	missense	Exon 1 of 11	NP_631913.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAD2	ENST00000315906.10	TSL:1 MANE Select	c.86C>A	p.Pro29His	missense	Exon 1 of 10	ENSP00000325153.6	Q8NCV1-1
	ADAD2	ENST00000268624.7	TSL:2	c.86C>A	p.Pro29His	missense	Exon 1 of 11	ENSP00000268624.3	Q8NCV1-2
	ADAD2	ENST00000922037.1		c.86C>A	p.Pro29His	missense	Exon 1 of 11	ENSP00000592096.1

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

African (AFR) AF: 0.00 AC: 0 AN: 32586

American (AMR) AF: 0.00 AC: 0 AN: 42176

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25612

East Asian (EAS) AF: 0.00 AC: 0 AN: 39118

South Asian (SAS) AF: 0.00 AC: 0 AN: 85500

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48090

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5088

European-Non Finnish (NFE) AF: 0.00000273 AC: 3 AN: 1099158

Other (OTH) AF: 0.00 AC: 0 AN: 59078

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.12
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.0080
Sift	Benign	0.087	T
Sift4G	Benign	0.35	T
Polyphen		0.0020	B
Vest4		0.19
MutPred		0.27		Gain of helix (P = 6e-04)
MVP		0.14
ClinPred		0.026	T
GERP RS		1.2
PromoterAI		-0.16	Neutral
Varity_R		0.055
gMVP		0.19
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs759599115; hg19: chr16-84224922;