10-1199981-G-A

Variant names:

• chr10-1199981-G-A
• rs139728897
• NM_018702.4:c.1849C>T

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.1849C>T​(p.Arg617Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000499 in 1,563,318 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R617Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000051 (0 hom.)
• Consequence: ADARB2 NM_018702.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.91
• 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=0.2418665).

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.1849C>T	p.Arg617Trp	missense	Exon 8 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.1849C>T	p.Arg617Trp	missense	Exon 8 of 10	ENSP00000370713.1	Q9NS39-1
	ADARB2	ENST00000381310.7	TSL:1	c.376C>T	p.Arg126Trp	missense	Exon 1 of 3	ENSP00000370711.3	Q9NS39-2
	ADARB2	ENST00000381305.1	TSL:2	c.55C>T	p.Arg19Trp	missense	Exon 2 of 4	ENSP00000370706.1	Q5VW43

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152196 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000283 AC: 6 AN: 212286 AF XY: 0.0000261

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000573

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000302

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000510 AC: 72 AN: 1411004 Hom.: 0 Cov.: 34 AF XY: 0.0000531 AC XY: 37 AN XY: 696282

African (AFR) AF: 0.00 AC: 0 AN: 32916

American (AMR) AF: 0.00 AC: 0 AN: 42940

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24678

East Asian (EAS) AF: 0.0000258 AC: 1 AN: 38816

South Asian (SAS) AF: 0.0000616 AC: 5 AN: 81196

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38292

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4202

European-Non Finnish (NFE) AF: 0.0000578 AC: 63 AN: 1089474

Other (OTH) AF: 0.0000513 AC: 3 AN: 58490

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152314 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74478

African (AFR) AF: 0.0000240 AC: 1 AN: 41588

American (AMR) AF: 0.00 AC: 0 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.0000378

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000249 AC: 3

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	0.089
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.71	D
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.088	D
MetaRNN	Benign	0.24	T
MetaSVM	Pathogenic	0.82	D
MutationAssessor	Uncertain	2.8	M
PhyloP100		3.9
PrimateAI	Benign	0.29	T
PROVEAN	Pathogenic	-5.9	D
REVEL	Pathogenic	0.66
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.26
MVP		0.66
MPC		0.31
ClinPred		0.89	D
GERP RS		2.8
PromoterAI		-0.030	Neutral
Varity_R		0.55
gMVP		0.44
Mutation Taster		=76/24	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: rs139728897; hg19: chr10-1245921;