10-1184934-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_018702.4(ADARB2):c.1970G>A(p.Arg657Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000701 in 1,613,926 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0033 (4 hom., cov: 34)
  • Exomes 𝑓: 0.00043 (8 hom.)
• Consequence: ADARB2 NM_018702.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.569

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 Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008507669).
• BP6: Variant 10-1184934-C-T is Benign according to our data. Variant chr10-1184934-C-T is described in ClinVar as [Benign]. Clinvar id is 790273.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADARB2	NM_018702.4	c.1970G>A	p.Arg657Gln	missense_variant	9/10	ENST00000381312.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADARB2	ENST00000381312.6	c.1970G>A	p.Arg657Gln	missense_variant	9/10	1	NM_018702.4	P1
LINC00200	ENST00000655745.1	n.264+24297C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00330 AC: 503 AN: 152252 Hom.: 4 Cov.: 34

Gnomad AFR AF: 0.0108

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00501

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00124 AC: 311 AN: 250442 Hom.: 6 AF XY: 0.00101 AC XY: 137 AN XY: 135566

Gnomad AFR exome AF: 0.0124

Gnomad AMR exome AF: 0.000550

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00436

Gnomad SAS exome AF: 0.0000654

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000354

Gnomad OTH exome AF: 0.000980

GnomAD4 exome AF: 0.000430 AC: 629 AN: 1461556 Hom.: 8 Cov.: 30 AF XY: 0.000381 AC XY: 277 AN XY: 727110

Gnomad4 AFR exome AF: 0.0128

Gnomad4 AMR exome AF: 0.000514

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00219

Gnomad4 SAS exome AF: 0.000151

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000144

Gnomad4 OTH exome AF: 0.000944

GnomAD4 genome AF: 0.00330 AC: 503 AN: 152370 Hom.: 4 Cov.: 34 AF XY: 0.00334 AC XY: 249 AN XY: 74518

Gnomad4 AFR AF: 0.0108

Gnomad4 AMR AF: 0.00131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00502

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000719 Hom.: 2

Bravo AF: 0.00382

ESP6500AA AF: 0.0132 AC: 58

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00126 AC: 153

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 27, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.22
Cadd	Benign	17
Dann	Uncertain	1.0
DEOGEN2	Uncertain	0.53	D;.;.
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.38	N
LIST_S2	Uncertain	0.90	D;D;D
MetaRNN	Benign	0.0085	T;T;T
MetaSVM	Uncertain	0.64	D
MutationAssessor	Uncertain	2.8	M;.;.
MutationTaster	Benign	0.86	D;D;D
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.9	N;N;N
REVEL	Uncertain	0.46
Sift	Uncertain	0.0030	D;T;D
Sift4G	Uncertain	0.0080	D;D;D
Polyphen		0.46	P;.;P
Vest4		0.27
MVP		0.44
MPC		0.62
ClinPred		0.047	T
GERP RS		-3.0
Varity_R		0.27
gMVP		0.41

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

LitVar

Other links and lift over

dbSNP: rs141298814; hg19: chr10-1230874; COSMIC: COSV67182069;