10-1184896-C-A

Variant names:

• chr10-1184896-C-A
• rs758258253
• NM_018702.4:c.2008G>T

Variant summary

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

The NM_018702.4(ADARB2):​c.2008G>T​(p.Val670Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 15/22 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. V670M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 34)
• Consequence: ADARB2 NM_018702.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.245
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.2008G>T	p.Val670Leu	missense	Exon 9 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.2008G>T	p.Val670Leu	missense	Exon 9 of 10	ENSP00000370713.1	Q9NS39-1
	ADARB2	ENST00000381310.7	TSL:1	c.535G>T	p.Val179Leu	missense	Exon 2 of 3	ENSP00000370711.3	Q9NS39-2
	ADARB2	ENST00000474762.5	TSL:1	n.208G>T		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	0.0056	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	8.6
DANN	Benign	0.89
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.74
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.61	T
M_CAP	Uncertain	0.088	D
MetaRNN	Uncertain	0.47	T
MetaSVM	Uncertain	-0.24	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.24
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.97	N
REVEL	Benign	0.21
Sift	Uncertain	0.021	D
Sift4G	Benign	0.078	T
Polyphen		0.0070	B
Vest4		0.12
MutPred		0.68		Gain of disorder (P = 0.0696)
MVP		0.40
MPC		0.32
ClinPred		0.17	T
GERP RS		1.2
Varity_R		0.10
gMVP		0.31
Mutation Taster		=92/8	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: rs758258253; hg19: chr10-1230836;