rs1403543

Positions:

• chrX-116170939-G-A
• chrX-116170939-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_000686.5(AGTR2):​c.-95-29G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 110,086 control chromosomes in the GnomAD database, including 9,476 homozygotes. There are 15,438 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.48 (9476 hom., 15438 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: AGTR2 NM_000686.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.165

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant X-116170939-G-A is Benign according to our data. Variant chrX-116170939-G-A is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.616 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGTR2	NM_000686.5	c.-95-29G>A		intron_variant		ENST00000371906.5	NP_000677.2
AGTR2	NM_001385624.1	c.-36+123G>A		intron_variant			NP_001372553.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGTR2	ENST00000371906.5	c.-95-29G>A		intron_variant		1	NM_000686.5	ENSP00000360973	P1
AGTR2	ENST00000681852.1	c.-36+123G>A		intron_variant				ENSP00000505750	P1

Frequencies

GnomAD3 genomes AF: 0.481 AC: 52933 AN: 110036 Hom.: 9479 Cov.: 23 AF XY: 0.476 AC XY: 15420 AN XY: 32390

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.627

Gnomad ASJ AF: 0.542

Gnomad EAS AF: 0.568

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.504

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.481 AC: 52941 AN: 110086 Hom.: 9476 Cov.: 23 AF XY: 0.476 AC XY: 15438 AN XY: 32452

Gnomad4 AFR AF: 0.346

Gnomad4 AMR AF: 0.628

Gnomad4 ASJ AF: 0.542

Gnomad4 EAS AF: 0.568

Gnomad4 SAS AF: 0.461

Gnomad4 FIN AF: 0.449

Gnomad4 NFE AF: 0.524

Gnomad4 OTH AF: 0.503

Alfa AF: 0.522 Hom.: 48607

Bravo AF: 0.491

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.0
DANN	Benign	0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1403543; hg19: chrX-115302192; COSMIC: COSV64156521;