rs1602586215

Variant names:

• chrX-116172370-G-A
• rs1602586215
• NM_000686.5:c.90G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-116172370-G-A
• chrX-116172370-G-C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_000686.5(AGTR2):​c.90G>A​(p.Glu30Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,097,613 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples 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: not found (cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: AGTR2 NM_000686.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.345
• Publications: 0 publications found

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]

AGTR2 Gene-Disease associations (from GenCC):

• non-syndromic X-linked intellectual disability

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
• X-linked complex neurodevelopmental disorder

  Inheritance: XL Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP7: Synonymous conserved (PhyloP=-0.345 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000686.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGTR2	NM_000686.5	MANE Select	c.90G>A	p.Glu30Glu	synonymous	Exon 3 of 3	NP_000677.2
	AGTR2	NM_001385624.1		c.90G>A	p.Glu30Glu	synonymous	Exon 2 of 2	NP_001372553.1	P50052

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGTR2	ENST00000371906.5	TSL:1 MANE Select	c.90G>A	p.Glu30Glu	synonymous	Exon 3 of 3	ENSP00000360973.4	P50052
	AGTR2	ENST00000681852.1		c.90G>A	p.Glu30Glu	synonymous	Exon 2 of 2	ENSP00000505750.1	P50052
	AGTR2	ENST00000971224.1		c.90G>A	p.Glu30Glu	synonymous	Exon 3 of 3	ENSP00000641283.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1097613 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 363143

African (AFR) AF: 0.00 AC: 0 AN: 26376

American (AMR) AF: 0.00 AC: 0 AN: 35152

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19365

East Asian (EAS) AF: 0.00 AC: 0 AN: 30191

South Asian (SAS) AF: 0.00 AC: 0 AN: 54134

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40518

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4135

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 841665

Other (OTH) AF: 0.00 AC: 0 AN: 46077

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.81
DANN	Benign	0.41
PhyloP100		-0.34

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: rs1602586215; hg19: chrX-115303623;