Genetic Variant AGTR2:c.*205A>G (chrX-116173577-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000686.5(AGTR2):c.*205A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. 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 0.51 ( 10440 hom., 16684 hem., cov: 23)

Exomes 𝑓: 0.55 ( 38837 hom. 61580 hem. )

Failed GnomAD Quality Control

Consequence

AGTR2
NM_000686.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.16

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 Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGTR2	NM_000686.5 link	c.*205A>G		3_prime_UTR_variant	Exon 3 of 3	ENST00000371906.5	NP_000677.2	P50052
AGTR2	NM_001385624.1 link	c.*205A>G		3_prime_UTR_variant	Exon 2 of 2		NP_001372553.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
AGTR2	ENST00000371906.5 link	c.*205A>G	3_prime_UTR_variant	Exon 3 of 3	1	NM_000686.5	ENSP00000360973.4	P50052
AGTR2	ENST00000681852.1 link	c.*205A>G	downstream_gene_variant				ENSP00000505750.1	P50052
AGTR2	ENST00000680409.1 link	n.*147A>G	downstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.507

AC:

56215

AN:

110787

Hom.:

10438

Cov.:

AF XY:

0.505

AC XY:

16668

AN XY:

33019

show subpopulations

Gnomad AFR

AF:

0.396

Gnomad AMI

AF:

0.556

Gnomad AMR

AF:

0.637

Gnomad ASJ

AF:

0.543

Gnomad EAS

AF:

0.590

Gnomad SAS

AF:

0.464

Gnomad FIN

AF:

0.530

Gnomad MID

AF:

0.504

Gnomad NFE

AF:

0.538

Gnomad OTH

AF:

0.535

GnomAD4 exome

AF:

0.546

AC:

204045

AN:

373677

Hom.:

38837

Cov.:

AF XY:

0.565

AC XY:

61580

AN XY:

109045

show subpopulations

Gnomad4 AFR exome

AF:

0.411

Gnomad4 AMR exome

AF:

0.654

Gnomad4 ASJ exome

AF:

0.550

Gnomad4 EAS exome

AF:

0.626

Gnomad4 SAS exome

AF:

0.499

Gnomad4 FIN exome

AF:

0.536

Gnomad4 NFE exome

AF:

0.545

Gnomad4 OTH exome

AF:

0.543

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.507

AC:

56232

AN:

110838

Hom.:

10440

Cov.:

AF XY:

0.504

AC XY:

16684

AN XY:

33080

show subpopulations

Gnomad4 AFR

AF:

0.396

Gnomad4 AMR

AF:

0.638

Gnomad4 ASJ

AF:

0.543

Gnomad4 EAS

AF:

0.590

Gnomad4 SAS

AF:

0.464

Gnomad4 FIN

AF:

0.530

Gnomad4 NFE

AF:

0.538

Gnomad4 OTH

AF:

0.536

Alfa

AF:

0.536

Hom.:

43266

Bravo

AF:

0.515

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.34

DANN

Benign

0.70

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over