16-84191238-C-G

Variant names:

• chr16-84191238-C-G
• rs1469832701
• NM_001145400.2:c.8C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001145400.2(ADAD2):​c.8C>G​(p.Ser3Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 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. S3L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 35)
• Consequence: ADAD2 NM_001145400.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04
• Publications: 1 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29963738).

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.8C>G	p.Ser3Trp	missense	Exon 1 of 10	NP_001138872.1	Q8NCV1-1
	ADAD2	NM_139174.4		c.8C>G	p.Ser3Trp	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.8C>G	p.Ser3Trp	missense	Exon 1 of 10	ENSP00000325153.6	Q8NCV1-1
	ADAD2	ENST00000268624.7	TSL:2	c.8C>G	p.Ser3Trp	missense	Exon 1 of 11	ENSP00000268624.3	Q8NCV1-2
	ADAD2	ENST00000922037.1		c.8C>G	p.Ser3Trp	missense	Exon 1 of 11	ENSP00000592096.1

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Cov.: 88

GnomAD4 genome Cov.: 35

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.0
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.12
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.47
MutPred		0.24		Loss of phosphorylation at S3 (P = 0.0075)
MVP		0.36
ClinPred		0.61	D
GERP RS		1.9
PromoterAI		-0.10	Neutral
Varity_R		0.069
gMVP		0.17

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: rs1469832701; hg19: chr16-84224844;