Genetic Variant NM_000686.5:c.*501A>C (chrX-116173873-A-C) – 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.*501A>C 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 ( 10429 hom., 16415 hem., cov: 23)

Exomes 𝑓: 0.54 ( 1749 hom. 2630 hem. )

Failed GnomAD Quality Control

Consequence

AGTR2
NM_000686.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.174

Publications

26 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=-0.9).

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGTR2	NM_000686.5 link	c.*501A>C		3_prime_UTR_variant	Exon 3 of 3	ENST00000371906.5	NP_000677.2	P50052
AGTR2	NM_001385624.1 link	c.*501A>C		3_prime_UTR_variant	Exon 2 of 2		NP_001372553.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGTR2	ENST00000371906.5 link	c.*501A>C		3_prime_UTR_variant	Exon 3 of 3	1	NM_000686.5	ENSP00000360973.4		P50052

Frequencies

GnomAD3 genomes

AF:

0.507

AC:

55920

AN:

110280

Hom.:

10427

Cov.:

show subpopulations

Gnomad AFR

AF:

0.395

Gnomad AMI

AF:

0.556

Gnomad AMR

AF:

0.636

Gnomad ASJ

AF:

0.542

Gnomad EAS

AF:

0.589

Gnomad SAS

AF:

0.464

Gnomad FIN

AF:

0.529

Gnomad MID

AF:

0.513

Gnomad NFE

AF:

0.538

Gnomad OTH

AF:

0.535

GnomAD4 exome

AF:

0.544

AC:

8937

AN:

16437

Hom.:

1749

Cov.:

AF XY:

0.551

AC XY:

2630

AN XY:

4771

show subpopulations

African (AFR)

AF:

0.368

AC:

AN:

American (AMR)

AF:

0.647

AC:

727

AN:

1124

Ashkenazi Jewish (ASJ)

AF:

0.392

AC:

AN:

East Asian (EAS)

AF:

0.636

AC:

159

AN:

250

South Asian (SAS)

AF:

0.470

AC:

238

AN:

506

European-Finnish (FIN)

AF:

0.544

AC:

6106

AN:

11229

Middle Eastern (MID)

AF:

0.636

AC:

AN:

European-Non Finnish (NFE)

AF:

0.515

AC:

1521

AN:

2955

Other (OTH)

AF:

0.521

AC:

152

AN:

292

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

146

293

439

586

732

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.507

AC:

55939

AN:

110336

Hom.:

10429

Cov.:

AF XY:

0.503

AC XY:

16415

AN XY:

32616

show subpopulations

African (AFR)

AF:

0.395

AC:

12028

AN:

30484

American (AMR)

AF:

0.637

AC:

6560

AN:

10293

Ashkenazi Jewish (ASJ)

AF:

0.542

AC:

1423

AN:

2626

East Asian (EAS)

AF:

0.588

AC:

2037

AN:

3462

South Asian (SAS)

AF:

0.464

AC:

1220

AN:

2632

European-Finnish (FIN)

AF:

0.529

AC:

3068

AN:

5796

Middle Eastern (MID)

AF:

0.505

AC:

107

AN:

212

European-Non Finnish (NFE)

AF:

0.538

AC:

28315

AN:

52650

Other (OTH)

AF:

0.535

AC:

806

AN:

1506

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

978

1956

2933

3911

4889

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.527

Hom.:

13722

Bravo

AF:

0.515

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.69

(source)

DANN

Benign

0.46

PhyloP100

-0.17

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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NM_000686.5:c.*501A>C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over