Variant X-116172437-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The ENST00000371906.5(AGTR2):c.157A>T(p.Ile53Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000745 in 1,208,338 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 27 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000079 ( 0 hom. 27 hem. )

Consequence

AGTR2
ENST00000371906.5 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 0.0760

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07511616).

BS2

High Hemizygotes in GnomAdExome4 at 27 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGTR2	NM_000686.5 linkuse as main transcript	c.157A>T	p.Ile53Phe	missense_variant	3/3	ENST00000371906.5	NP_000677.2
AGTR2	NM_001385624.1 linkuse as main transcript	c.157A>T	p.Ile53Phe	missense_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.157A>T	p.Ile53Phe	missense_variant	3/3	1	NM_000686.5	ENSP00000360973	P1
AGTR2	ENST00000681852.1 linkuse as main transcript	c.157A>T	p.Ile53Phe	missense_variant	2/2			ENSP00000505750	P1
AGTR2	ENST00000680409.1 linkuse as main transcript	n.625A>T		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.0000269

AC:

AN:

111513

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33743

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000334

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000115

AC:

AN:

182989

Hom.:

AF XY:

0.0000887

AC XY:

AN XY:

67619

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000625

Gnomad NFE exome

AF:

0.000135

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000793

AC:

AN:

1096825

Hom.:

Cov.:

AF XY:

0.0000745

AC XY:

AN XY:

362343

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000469

Gnomad4 NFE exome

AF:

0.0000761

Gnomad4 OTH exome

AF:

0.0000869

GnomAD4 genome

AF:

0.0000269

AC:

AN:

111513

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33743

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000334

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000416

ExAC

AF:

0.0000988

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

OMIM

Aug 08, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.33

CADD

Benign

7.2

DANN

Benign

0.95

DEOGEN2

Benign

0.34

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.58

M_CAP

Benign

0.0062

MetaRNN

Benign

0.075

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

MutationTaster

Benign

0.99

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.9

REVEL

Uncertain

0.31

Sift

Benign

0.25

Sift4G

Benign

0.23

Polyphen

0.0

Vest4

0.16

MVP

0.90

MPC

0.23

ClinPred

0.031

GERP RS

3.3

Varity_R

0.37

gMVP

0.36

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