rs17231478

Variant names:

• chrX-116174557-G-T
• rs17231478
• NM_000686.5:c.*1185G>T

Variant summary

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

The NM_000686.5(AGTR2):​c.*1185G>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 0.0351 in 122,611 control chromosomes in the GnomAD database, including 81 homozygotes. There are 1,226 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 0.034 (74 hom., 1061 hem., cov: 22)
  • Exomes 𝑓: 0.044 (7 hom. 165 hem.)
• Consequence: AGTR2 NM_000686.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.051 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGTR2	NM_000686.5	c.*1185G>T		3_prime_UTR_variant	Exon 3 of 3	ENST00000371906.5	NP_000677.2
AGTR2	NM_001385624.1	c.*1185G>T		3_prime_UTR_variant	Exon 2 of 2		NP_001372553.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGTR2	ENST00000371906.5	c.*1185G>T		3_prime_UTR_variant	Exon 3 of 3	1	NM_000686.5	ENSP00000360973.4

Frequencies

GnomAD3 genomes AF: 0.0343 AC: 3814 AN: 111210 Hom.: 74 Cov.: 22 AF XY: 0.0318 AC XY: 1063 AN XY: 33446

Gnomad AFR AF: 0.00629

Gnomad AMI AF: 0.0102

Gnomad AMR AF: 0.0326

Gnomad ASJ AF: 0.0379

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0147

Gnomad FIN AF: 0.0476

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0527

Gnomad OTH AF: 0.0379

GnomAD4 exome AF: 0.0436 AC: 495 AN: 11347 Hom.: 7 Cov.: 0 AF XY: 0.0468 AC XY: 165 AN XY: 3527

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0437

Gnomad4 NFE exome AF: 0.0411

Gnomad4 OTH exome AF: 0.0423

GnomAD4 genome AF: 0.0342 AC: 3809 AN: 111264 Hom.: 74 Cov.: 22 AF XY: 0.0317 AC XY: 1061 AN XY: 33510

Gnomad4 AFR AF: 0.00628

Gnomad4 AMR AF: 0.0326

Gnomad4 ASJ AF: 0.0379

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0143

Gnomad4 FIN AF: 0.0476

Gnomad4 NFE AF: 0.0526

Gnomad4 OTH AF: 0.0374

Alfa AF: 0.0414 Hom.: 563

Bravo AF: 0.0338

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.010
DANN	Benign	0.43

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: rs17231478; hg19: chrX-115305810;