chr10-1183345-C-T

Variant names:

• chr10-1183345-C-T
• NM_018702.4:c.2068G>A

Variant summary

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

The NM_018702.4(ADARB2):​c.2068G>A​(p.Gly690Arg) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ADARB2 NM_018702.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.708
• Publications: 0 publications found

Genes affected

ADARB2 (HGNC:227): (adenosine deaminase RNA specific B2 (inactive)) This gene encodes a member of the double-stranded RNA adenosine deaminase family of RNA-editing enzymes and may play a regulatory role in RNA editing. [provided by RefSeq, Jul 2008]

LINC00200 (HGNC:30974): (long intergenic non-protein coding RNA 200)

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=0.1517705).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018702.4. 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
	ADARB2	NM_018702.4	MANE Select	c.2068G>A	p.Gly690Arg	missense	Exon 10 of 10	NP_061172.1	Q9NS39-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADARB2	ENST00000381312.6	TSL:1 MANE Select	c.2068G>A	p.Gly690Arg	missense	Exon 10 of 10	ENSP00000370713.1	Q9NS39-1
	ADARB2	ENST00000381310.7	TSL:1	c.595G>A	p.Gly199Arg	missense	Exon 3 of 3	ENSP00000370711.3	Q9NS39-2
	ADARB2	ENST00000474762.5	TSL:1	n.268G>A		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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	0.083
BayesDel_addAF	Benign	0.0099	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	13
DANN	Benign	0.96
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.69	T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.15	T
MetaSVM	Uncertain	0.078	D
MutationAssessor	Benign	1.7	L
PhyloP100		0.71
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.070	N
REVEL	Benign	0.24
Sift	Benign	0.43	T
Sift4G	Benign	0.54	T
Polyphen		0.0050	B
Vest4		0.13
MutPred		0.43		Gain of solvent accessibility (P = 0.0037)
MVP		0.27
MPC		0.70
ClinPred		0.15	T
GERP RS		4.4
Varity_R		0.062
gMVP		0.43
Mutation Taster		=89/11	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

hg19: chr10-1229285; COSMIC: COSV67181948;