rs35474657

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_000686.5(AGTR2):c.971G>A(p.Arg324Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000373 in 1,209,444 control chromosomes in the GnomAD database, including 1 homozygotes. There are 115 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0022 ( 1 hom., 58 hem., cov: 22)

Exomes 𝑓: 0.00019 ( 0 hom. 57 hem. )

Consequence

AGTR2
NM_000686.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity no assertion criteria provided U:1B:1

Conservation

PhyloP100: 4.59

Publications

9 publications found

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 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

AGTR2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.05501291).

BP6

Variant X-116173251-G-A is Benign according to our data. Variant chrX-116173251-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 11718.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Hemizygotes in GnomAd4 at 58 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGTR2	NM_000686.5 link	c.971G>A	p.Arg324Gln	missense_variant	Exon 3 of 3	ENST00000371906.5	NP_000677.2	P50052
AGTR2	NM_001385624.1 link	c.971G>A	p.Arg324Gln	missense_variant	Exon 2 of 2		NP_001372553.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
AGTR2	ENST00000371906.5 link	c.971G>A	p.Arg324Gln	missense_variant	Exon 3 of 3	1	NM_000686.5	ENSP00000360973.4	P50052
AGTR2	ENST00000681852.1 link	c.971G>A	p.Arg324Gln	missense_variant	Exon 2 of 2			ENSP00000505750.1	P50052
AGTR2	ENST00000680409.1 link	n.1439G>A		non_coding_transcript_exon_variant	Exon 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.00214

AC:

238

AN:

111443

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00748

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000385

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:

0.0000377

Gnomad OTH

AF:

0.00203

GnomAD2 exomes

AF:

0.000552

AC:

101

AN:

183068

AF XY:

0.000384

show subpopulations

Gnomad AFR exome

AF:

0.00722

Gnomad AMR exome

AF:

0.000110

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000123

Gnomad OTH exome

AF:

0.000443

GnomAD4 exome

AF:

0.000192

AC:

211

AN:

1097949

Hom.:

Cov.:

AF XY:

0.000157

AC XY:

AN XY:

363421

show subpopulations

African (AFR)

AF:

0.00713

AC:

188

AN:

26378

American (AMR)

AF:

0.000142

AC:

AN:

35185

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19368

East Asian (EAS)

AF:

0.00

AC:

AN:

30203

South Asian (SAS)

AF:

0.0000185

AC:

AN:

54132

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40532

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4137

European-Non Finnish (NFE)

AF:

0.00000713

AC:

AN:

841927

Other (OTH)

AF:

0.000239

AC:

AN:

46087

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00215

AC:

240

AN:

111495

Hom.:

Cov.:

AF XY:

0.00172

AC XY:

AN XY:

33731

show subpopulations

African (AFR)

AF:

0.00752

AC:

231

AN:

30700

American (AMR)

AF:

0.000384

AC:

AN:

10405

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2646

East Asian (EAS)

AF:

0.00

AC:

AN:

3519

South Asian (SAS)

AF:

0.00

AC:

AN:

2691

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6042

Middle Eastern (MID)

AF:

0.00

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.0000377

AC:

AN:

53093

Other (OTH)

AF:

0.00200

AC:

AN:

1500

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000568

Hom.:

Bravo

AF:

0.00216

ESP6500AA

AF:

0.00730

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000692

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Aug 08, 2013

OMIM

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:literature only

- -

AGTR2-related disorder

Benign:1

Dec 23, 2019

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.76

CADD

Benign

(source)

DANN

Benign

0.76

DEOGEN2

Benign

0.17

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.79

M_CAP

Benign

0.0024

MetaRNN

Benign

0.055

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

4.6

PrimateAI

Benign

0.34

PROVEAN

Benign

0.0

REVEL

Benign

0.086

Sift

Benign

0.83

Sift4G

Benign

0.68

Polyphen

0.012

Vest4

0.082

MVP

0.82

MPC

0.16

ClinPred

0.016

GERP RS

1.7

Varity_R

0.19

gMVP

0.24

Mutation Taster

=91/9

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over