X-116174475-G-C

Position:

• chrX-116174475-G-C

Variant summary

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

The ENST00000371906.5(AGTR2):​c.*1103G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 120,685 control chromosomes in the GnomAD database, including 2,658 homozygotes. There are 8,089 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 0.24 (2377 hom., 7194 hem., cov: 21)
  • Exomes 𝑓: 0.26 (281 hom. 895 hem.)
• Consequence: AGTR2 ENST00000371906.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.481

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGTR2	NM_000686.5	c.*1103G>C		3_prime_UTR_variant	3/3	ENST00000371906.5	NP_000677.2
AGTR2	NM_001385624.1	c.*1103G>C		3_prime_UTR_variant	2/2		NP_001372553.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGTR2	ENST00000371906.5	c.*1103G>C		3_prime_UTR_variant	3/3	1	NM_000686.5	ENSP00000360973	P1

Frequencies

GnomAD3 genomes AF: 0.239 AC: 26095 AN: 109282 Hom.: 2380 Cov.: 21 AF XY: 0.227 AC XY: 7184 AN XY: 31652

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.249

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.250

GnomAD4 exome AF: 0.260 AC: 2953 AN: 11353 Hom.: 281 Cov.: 0 AF XY: 0.254 AC XY: 895 AN XY: 3529

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.333

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.261

Gnomad4 NFE exome AF: 0.200

Gnomad4 OTH exome AF: 0.208

GnomAD4 genome AF: 0.239 AC: 26093 AN: 109332 Hom.: 2377 Cov.: 21 AF XY: 0.227 AC XY: 7194 AN XY: 31712

Gnomad4 AFR AF: 0.262

Gnomad4 AMR AF: 0.177

Gnomad4 ASJ AF: 0.220

Gnomad4 EAS AF: 0.181

Gnomad4 SAS AF: 0.263

Gnomad4 FIN AF: 0.236

Gnomad4 NFE AF: 0.241

Gnomad4 OTH AF: 0.246

Alfa AF: 0.118 Hom.: 580

Bravo AF: 0.238

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.13
DANN	Benign	0.42

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: rs12845035; hg19: chrX-115305728;