16-84191528-C-T

Variant names:

• chr16-84191528-C-T
• rs997900127
• NM_001145400.2:c.298C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001145400.2(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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P100R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: ADAD2 NM_001145400.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.60
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14161703).

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.298C>T	p.Pro100Ser	missense	Exon 1 of 10	NP_001138872.1	Q8NCV1-1
	ADAD2	NM_139174.4		c.298C>T	p.Pro100Ser	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.298C>T	p.Pro100Ser	missense	Exon 1 of 10	ENSP00000325153.6	Q8NCV1-1
	ADAD2	ENST00000268624.7	TSL:2	c.298C>T	p.Pro100Ser	missense	Exon 1 of 11	ENSP00000268624.3	Q8NCV1-2
	ADAD2	ENST00000922037.1		c.298C>T	p.Pro100Ser	missense	Exon 1 of 11	ENSP00000592096.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.0000143 AC: 20 AN: 1394016 Hom.: 0 Cov.: 38 AF XY: 0.00000727 AC XY: 5 AN XY: 687732

African (AFR) AF: 0.0000317 AC: 1 AN: 31556

American (AMR) AF: 0.00 AC: 0 AN: 35372

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25100

East Asian (EAS) AF: 0.00 AC: 0 AN: 35724

South Asian (SAS) AF: 0.00 AC: 0 AN: 79194

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44948

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5682

European-Non Finnish (NFE) AF: 0.0000167 AC: 18 AN: 1078542

Other (OTH) AF: 0.0000173 AC: 1 AN: 57898

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.25	T
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	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
PhyloP100		1.6
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.78	N
REVEL	Benign	0.069
Sift	Benign	0.041	D
Sift4G	Benign	0.45	T
Polyphen		0.97	D
Vest4		0.096
MutPred		0.41		Loss of catalytic residue at P100 (P = 0.0026)
MVP		0.36
ClinPred		0.23	T
GERP RS		3.1
PromoterAI		0.0013	Neutral
Varity_R		0.033
gMVP		0.29
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs997900127; hg19: chr16-84225134;