rs34303217

Variant names:

• chr10-111079524-T-A
• rs34303217
• NM_000681.4:c.*130T>A

Your query was ambiguous. Multiple possible variants found:

• chr10-111079524-T-A
• chr10-111079524-T-C
• chr10-111079524-T-G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BS1 BS2_Supporting

The NM_000681.4(ADRA2A):​c.*130T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00178 in 988,308 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0075 (10 hom., cov: 33)
  • Exomes 𝑓: 0.00074 (8 hom.)
• Consequence: ADRA2A NM_000681.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.38
• Publications: 4 publications found

Genes affected

ADRA2A (HGNC:281): (adrenoceptor alpha 2A) Alpha-2-adrenergic receptors are members of the G protein-coupled receptor superfamily. The alpha-2-adrenergic receptors are a type of adrenergic receptors (for adrenaline or epinephrine), which inhibit adenylate cyclase. These receptors include 3 highly homologous subtypes: alpha2A, alpha2B, and alpha2C. They are involved in regulating the release of neurotransmitter molecules from sympathetic nerves and from adrenergic neurons in the central nervous system. The sympathetic nervous system regulates cardiovascular function by activating adrenergic receptors in the heart, blood vessels and kidney. Studies in mouse revealed that both the alpha2A and alpha2C receptor subtypes were required for presynaptic transmitter release from the sympathetic nervous system in the heart and from central noradrenergic neurons. The alpha-2-adrenergic receptors are also involved in catecholamine signaling by extracellular regulated protein kinase 1 and 2 (ERK1/2) pathways. A clear association between the alpha-2-adrenergic receptor and disease has not been yet established. [provided by RefSeq, Sep 2019]

ADRA2A Gene-Disease associations (from GenCC):

• lipodystrophy

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• lipodystrophy, familial partial, type 8

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00751 (1144/152342) while in subpopulation AFR AF = 0.0261 (1084/41580). AF 95% confidence interval is 0.0248. There are 10 homozygotes in GnomAd4. There are 561 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1144 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000681.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADRA2A	NM_000681.4	MANE Select	c.*130T>A		3_prime_UTR	Exon 1 of 1	NP_000672.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADRA2A	ENST00000280155.4	TSL:6 MANE Select	c.*130T>A		3_prime_UTR	Exon 1 of 1	ENSP00000280155.2

Frequencies

GnomAD3 genomes AF: 0.00746 AC: 1135 AN: 152224 Hom.: 10 Cov.: 33

Gnomad AFR AF: 0.0259

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00307

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00574

GnomAD4 exome AF: 0.000736 AC: 615 AN: 835966 Hom.: 8 Cov.: 11 AF XY: 0.000714 AC XY: 302 AN XY: 423170

African (AFR) AF: 0.0249 AC: 492 AN: 19746

American (AMR) AF: 0.00166 AC: 41 AN: 24708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16710

East Asian (EAS) AF: 0.00 AC: 0 AN: 34338

South Asian (SAS) AF: 0.0000874 AC: 5 AN: 57184

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46128

Middle Eastern (MID) AF: 0.000370 AC: 1 AN: 2702

European-Non Finnish (NFE) AF: 0.0000168 AC: 10 AN: 595782

Other (OTH) AF: 0.00171 AC: 66 AN: 38668

GnomAD4 genome AF: 0.00751 AC: 1144 AN: 152342 Hom.: 10 Cov.: 33 AF XY: 0.00753 AC XY: 561 AN XY: 74496

African (AFR) AF: 0.0261 AC: 1084 AN: 41580

American (AMR) AF: 0.00307 AC: 47 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68028

Other (OTH) AF: 0.00568 AC: 12 AN: 2114

Alfa AF: 0.000140 Hom.: 0

Bravo AF: 0.00859

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.47
DANN	Benign	0.78
PhyloP100		-2.4
Mutation Taster		=100/0	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: rs34303217; hg19: chr10-112839282;