rs5193

Positions:

• chrX-116173571-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000686.5(AGTR2):​c.*199G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 512,637 control chromosomes in the GnomAD database, including 11,781 homozygotes. There are 36,739 hemizygotes in GnomAD. 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 0.19 (1881 hom., 6610 hem., cov: 23)
  • Exomes 𝑓: 0.26 (9900 hom. 30129 hem.)
• Consequence: AGTR2 NM_000686.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.375

Genes affected

AGTR2 (HGNC:338): (angiotensin II receptor type 2) The protein encoded by this gene belongs to the G-protein coupled receptor 1 family, and functions as a receptor for angiotensin II. It is an intergral membrane protein that is highly expressed in fetus and in neonates, but scantily in adult tissues, except brain, adrenal medulla, and atretic ovary. This receptor has been shown to mediate programmed cell death and this apoptotic function may play an important role in developmental biology and pathophysiology. Mutations in this gene are been associated with X-linked cognitive disability. Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and SARS-CoV-2 infection results in down-regulation of angiotensin converting enzyme-2 (ACE2) receptors, the effects of which, triggers serious inflammatory lesions in the tissues involved, primarily in the lungs. The inflammatory reaction appears to be mediated by angiotensin II derivatives, including the angiotensin AT2 receptor which has been found to be upregulated in bronchoalveolar lavage samples from Coronavirus disease 2019 (COVID19) patients. [provided by RefSeq, Jul 2020]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGTR2	NM_000686.5	c.*199G>T		3_prime_UTR_variant	3/3	ENST00000371906.5
AGTR2	NM_001385624.1	c.*199G>T		3_prime_UTR_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGTR2	ENST00000371906.5	c.*199G>T		3_prime_UTR_variant	3/3	1	NM_000686.5	P1

Frequencies

GnomAD3 genomes AF: 0.194 AC: 21552 AN: 111366 Hom.: 1880 Cov.: 23 AF XY: 0.197 AC XY: 6612 AN XY: 33588

Gnomad AFR AF: 0.0345

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.258

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.209

GnomAD4 exome AF: 0.257 AC: 103175 AN: 401218 Hom.: 9900 Cov.: 6 AF XY: 0.274 AC XY: 30129 AN XY: 109926

Gnomad4 AFR exome AF: 0.0370

Gnomad4 AMR exome AF: 0.204

Gnomad4 ASJ exome AF: 0.276

Gnomad4 EAS exome AF: 0.179

Gnomad4 SAS exome AF: 0.192

Gnomad4 FIN exome AF: 0.375

Gnomad4 NFE exome AF: 0.268

Gnomad4 OTH exome AF: 0.243

GnomAD4 genome AF: 0.193 AC: 21547 AN: 111419 Hom.: 1881 Cov.: 23 AF XY: 0.196 AC XY: 6610 AN XY: 33651

Gnomad4 AFR AF: 0.0344

Gnomad4 AMR AF: 0.205

Gnomad4 ASJ AF: 0.262

Gnomad4 EAS AF: 0.154

Gnomad4 SAS AF: 0.176

Gnomad4 FIN AF: 0.380

Gnomad4 NFE AF: 0.261

Gnomad4 OTH AF: 0.207

Alfa AF: 0.241 Hom.: 10293

Bravo AF: 0.178

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.62
DANN	Benign	0.61

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: rs5193; hg19: chrX-115304824;