2-96115455-G-T

Variant names:

• chr2-96115455-G-T
• rs1049900125
• NM_000682.7:c.695C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000682.7(ADRA2B):​c.695C>A​(p.Ala232Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,742 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ADRA2B NM_000682.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.76

Genes affected

ADRA2B (HGNC:282): (adrenoceptor alpha 2B) This intronless gene encodes a seven-pass transmembrane protein. This protein is a member of a subfamily of G protein-coupled receptors that regulate neurotransmitter release from sympathetic nerves and from adrenergic neurons in the central nervous system. [provided by RefSeq, Apr 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1361751).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADRA2B	NM_000682.7	c.695C>A	p.Ala232Asp	missense_variant	Exon 1 of 1	ENST00000620793.2	NP_000673.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADRA2B	ENST00000620793.2	c.695C>A	p.Ala232Asp	missense_variant	Exon 1 of 1	6	NM_000682.7	ENSP00000480573.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000404 AC: 1 AN: 247794 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 134756

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000893

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1460742 Hom.: 0 Cov.: 38 AF XY: 0.00000275 AC XY: 2 AN XY: 726590

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000761 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.090	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	15
DANN	Benign	0.79
DEOGEN2	Benign	0.067	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.65
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	1.7	L
PrimateAI	Benign	0.38	T
Sift4G	Benign	0.20	T
Polyphen		0.14	B
Vest4		0.24
MutPred		0.37		Loss of loop (P = 9e-04);
MVP		0.43
ClinPred		0.11	T
GERP RS		2.6
Varity_R		0.19
gMVP		0.62

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: rs1049900125; hg19: chr2-96781194;