dbSNP rs1403543: AGTR2:c.-95-29G>A (chrX-116170939-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.48 ( 9476 hom., 15438 hem., cov: 23)

Failed GnomAD Quality Control

Consequence

AGTR2
NM_000686.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.165

Publications

60 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

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 rank	MANE	Protein	UniProt
AGTR2	NM_000686.5 link	c.-95-29G>A		intron_variant	Intron 1 of 2	ENST00000371906.5	NP_000677.2	P50052
AGTR2	NM_001385624.1 link	c.-36+123G>A		intron_variant	Intron 1 of 1		NP_001372553.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGTR2	ENST00000371906.5 link	c.-95-29G>A		intron_variant	Intron 1 of 2	1	NM_000686.5	ENSP00000360973.4		P50052
AGTR2	ENST00000681852.1 link	c.-36+123G>A		intron_variant	Intron 1 of 1			ENSP00000505750.1		P50052

Frequencies

GnomAD3 genomes

AF:

0.481

AC:

52933

AN:

110036

Hom.:

9479

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.481

AC:

52941

AN:

110086

Hom.:

9476

Cov.:

AF XY:

0.476

AC XY:

15438

AN XY:

32452

show subpopulations

African (AFR)

AF:

0.346

AC:

10518

AN:

30391

American (AMR)

AF:

0.628

AC:

6428

AN:

10230

Ashkenazi Jewish (ASJ)

AF:

0.542

AC:

1418

AN:

2616

East Asian (EAS)

AF:

0.568

AC:

1968

AN:

3463

South Asian (SAS)

AF:

0.461

AC:

1210

AN:

2627

European-Finnish (FIN)

AF:

0.449

AC:

2599

AN:

5784

Middle Eastern (MID)

AF:

0.493

AC:

106

AN:

215

European-Non Finnish (NFE)

AF:

0.524

AC:

27581

AN:

52588

Other (OTH)

AF:

0.503

AC:

752

AN:

1495

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

969

1938

2907

3876

4845

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

504

1008

1512

2016

2520

<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:

0.511

Hom.:

64602

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

(source)

DANN

Benign

0.32

PhyloP100

0.17

PromoterAI

-0.042

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over