10-1200048-G-C

Variant names:

• chr10-1200048-G-C
• NM_018702.4:c.1782C>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_018702.4(ADARB2):​c.1782C>G​(p.His594Gln) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ADARB2 NM_018702.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.28

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.919

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADARB2	NM_018702.4	c.1782C>G	p.His594Gln	missense_variant	Exon 8 of 10	ENST00000381312.6	NP_061172.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADARB2	ENST00000381312.6	c.1782C>G	p.His594Gln	missense_variant	Exon 8 of 10	1	NM_018702.4	ENSP00000370713.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 11, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1782C>G (p.H594Q) alteration is located in exon 8 (coding exon 8) of the ADARB2 gene. This alteration results from a C to G substitution at nucleotide position 1782, causing the histidine (H) at amino acid position 594 to be replaced by a glutamine (Q). 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	Pathogenic	0.90
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.59	D;.
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Pathogenic	0.29	D
MetaRNN	Pathogenic	0.92	D;D
MetaSVM	Pathogenic	0.86	D
MutationAssessor	Pathogenic	3.1	M;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Pathogenic	-7.7	D;D
REVEL	Pathogenic	0.77
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.0060	D;T
Polyphen		1.0	D;.
Vest4		0.81
MutPred		0.70		Gain of MoRF binding (P = 0.0763);.;
MVP		0.80
MPC		0.82
ClinPred		1.0	D
GERP RS		2.9
Varity_R		0.91
gMVP		0.65

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: chr10-1245988;