10-1183309-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018702.4(ADARB2):c.2104G>C(p.Gly702Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 3.25

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADARB2	NM_018702.4	c.2104G>C	p.Gly702Arg	missense_variant	10/10	ENST00000381312.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADARB2	ENST00000381312.6	c.2104G>C	p.Gly702Arg	missense_variant	10/10	1	NM_018702.4	P1
LINC00200	ENST00000655745.1	n.264+22672C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 19, 2022

The c.2104G>C (p.G702R) alteration is located in exon 10 (coding exon 10) of the ADARB2 gene. This alteration results from a G to C substitution at nucleotide position 2104, causing the glycine (G) at amino acid position 702 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
Cadd	Uncertain	24
Dann	Pathogenic	1.0
DEOGEN2	Benign	0.15	T;.;.
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Uncertain	0.18	D
MetaRNN	Uncertain	0.52	D;D;D
MetaSVM	Uncertain	0.77	D
MutationAssessor	Benign	1.4	L;.;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-2.4	N;D;D
REVEL	Uncertain	0.57
Sift	Benign	0.15	T;T;D
Sift4G	Benign	0.27	T;T;D
Polyphen		0.30	B;.;B
Vest4		0.24
MutPred		0.81		Gain of MoRF binding (P = 0.0343);.;.;
MVP		0.56
MPC		0.93
ClinPred		0.96	D
GERP RS		5.3
Varity_R		0.50
gMVP		0.56

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-1229249;