chr10-1363207-C-G

Variant names:

• chr10-1363207-C-G
• rs191180422
• NM_018702.4:c.898G>C

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.898G>C​(p.Glu300Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000757 in 1,321,446 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. 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. E300K) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: ADARB2 NM_018702.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.18
• 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]

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=0.13796994).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADARB2	NM_018702.4	c.898G>C	p.Glu300Gln	missense_variant	Exon 3 of 10	ENST00000381312.6	NP_061172.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADARB2	ENST00000381312.6	c.898G>C	p.Glu300Gln	missense_variant	Exon 3 of 10	1	NM_018702.4	ENSP00000370713.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.57e-7 AC: 1 AN: 1321446 Hom.: 0 Cov.: 32 AF XY: 0.00000153 AC XY: 1 AN XY: 654280

African (AFR) AF: 0.00 AC: 0 AN: 27028

American (AMR) AF: 0.00 AC: 0 AN: 30422

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22516

East Asian (EAS) AF: 0.00 AC: 0 AN: 29526

South Asian (SAS) AF: 0.00 AC: 0 AN: 71392

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34560

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5418

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1046670

Other (OTH) AF: 0.0000185 AC: 1 AN: 53914

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	18
DANN	Benign	0.94
DEOGEN2	Benign	0.040	T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.65
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	0.82	L
PhyloP100		3.2
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.92	N
REVEL	Benign	0.17
Sift	Benign	0.12	T
Sift4G	Benign	0.29	T
Polyphen		0.076	B
Vest4		0.15
MutPred		0.30		Gain of MoRF binding (P = 0.0325);
MVP		0.36
MPC		1.0
ClinPred		0.35	T
GERP RS		3.3
Varity_R		0.062
gMVP		0.39
Mutation Taster		=90/10	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: rs191180422; hg19: chr10-1405402;