Variant X-116172674-A-AT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PVS1_StrongBS2

The NM_000686.5(AGTR2):c.402dup(p.Ile135TyrfsTer7) variant causes a frameshift change. The variant allele was found at a frequency of 0.000441 in 1,208,111 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 162 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00035 ( 0 hom., 9 hem., cov: 23)

Exomes 𝑓: 0.00045 ( 0 hom. 153 hem. )

Consequence

AGTR2
NM_000686.5 frameshift

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.16

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.639 CDS is truncated, and there are 0 pathogenic variants in the truncated region.

BS2

High Hemizygotes in GnomAd4 at 9 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGTR2	NM_000686.5 linkuse as main transcript	c.402dup	p.Ile135TyrfsTer7	frameshift_variant	3/3	ENST00000371906.5	NP_000677.2
AGTR2	NM_001385624.1 linkuse as main transcript	c.402dup	p.Ile135TyrfsTer7	frameshift_variant	2/2		NP_001372553.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
AGTR2	ENST00000371906.5 linkuse as main transcript	c.402dup	p.Ile135TyrfsTer7	frameshift_variant	3/3	1	NM_000686.5	ENSP00000360973	P1
AGTR2	ENST00000681852.1 linkuse as main transcript	c.402dup	p.Ile135TyrfsTer7	frameshift_variant	2/2			ENSP00000505750	P1
AGTR2	ENST00000680409.1 linkuse as main transcript	n.870dup		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.000353

AC:

AN:

110551

Hom.:

Cov.:

AF XY:

0.000274

AC XY:

AN XY:

32889

show subpopulations

Gnomad AFR

AF:

0.0000989

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000774

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000530

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000350

AC:

AN:

182958

Hom.:

AF XY:

0.000370

AC XY:

AN XY:

67596

show subpopulations

Gnomad AFR exome

AF:

0.000152

Gnomad AMR exome

AF:

0.000219

Gnomad ASJ exome

AF:

0.000134

Gnomad EAS exome

AF:

0.0000722

Gnomad SAS exome

AF:

0.000262

Gnomad FIN exome

AF:

0.0000627

Gnomad NFE exome

AF:

0.000576

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.000450

AC:

494

AN:

1097560

Hom.:

Cov.:

AF XY:

0.000421

AC XY:

153

AN XY:

363022

show subpopulations

Gnomad4 AFR exome

AF:

0.000265

Gnomad4 AMR exome

AF:

0.000256

Gnomad4 ASJ exome

AF:

0.000103

Gnomad4 EAS exome

AF:

0.0000331

Gnomad4 SAS exome

AF:

0.000148

Gnomad4 FIN exome

AF:

0.0000740

Gnomad4 NFE exome

AF:

0.000534

Gnomad4 OTH exome

AF:

0.000326

GnomAD4 genome

AF:

0.000353

AC:

AN:

110551

Hom.:

Cov.:

AF XY:

0.000274

AC XY:

AN XY:

32889

show subpopulations

Gnomad4 AFR

AF:

0.0000989

Gnomad4 AMR

AF:

0.000774

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000530

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000442

EpiCase

AF:

0.000764

EpiControl

AF:

0.000474

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Revvity Omics, Revvity

May 06, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over