Variant 14-96240629-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001379692.1(BDKRB2):c.301G>A(p.Ala101Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000284 in 1,549,472 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

BDKRB2
NM_001379692.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.248

Variant links:

Genes affected

BDKRB2 (HGNC:1030): (bradykinin receptor B2) This gene encodes a receptor for bradykinin. The 9 aa bradykinin peptide elicits many responses including vasodilation, edema, smooth muscle spasm and pain fiber stimulation. Bradykinin is released upon activation by pathophysiologic conditions such as trauma and inflammation, and binds to its kinin receptors, B1 and B2. The B2 receptor associates with G proteins that stimulate a phosphatidylinositol-calcium second messenger system. [provided by RefSeq, Apr 2020]

BDKRB2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.098508894).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BDKRB2	NM_001379692.1 linkuse as main transcript	c.301G>A	p.Ala101Thr	missense_variant	3/3	ENST00000554311.2
BDKRB2	NM_000623.4 linkuse as main transcript	c.301G>A	p.Ala101Thr	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BDKRB2	ENST00000554311.2 linkuse as main transcript	c.301G>A	p.Ala101Thr	missense_variant	3/3	1	NM_001379692.1	P1	P30411-1
BDKRB2	ENST00000542454.2 linkuse as main transcript	c.220G>A	p.Ala74Thr	missense_variant	3/3	1			P30411-2
BDKRB2	ENST00000539359.1 linkuse as main transcript	c.220G>A	p.Ala74Thr	missense_variant	4/4	2			P30411-2

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000103

AC:

AN:

194950

Hom.:

AF XY:

0.0000583

AC XY:

AN XY:

102932

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000439

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000561

Gnomad FIN exome

AF:

0.0000554

Gnomad NFE exome

AF:

0.0000543

Gnomad OTH exome

AF:

0.000432

GnomAD4 exome

AF:

0.0000286

AC:

AN:

1397396

Hom.:

Cov.:

AF XY:

0.0000290

AC XY:

AN XY:

688770

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000261

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000510

Gnomad4 SAS exome

AF:

0.0000404

Gnomad4 FIN exome

AF:

0.0000395

Gnomad4 NFE exome

AF:

0.0000194

Gnomad4 OTH exome

AF:

0.0000520

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152076

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000479

Bravo

AF:

0.0000264

ExAC

AF:

0.0000908

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 17, 2021

The c.301G>A (p.A101T) alteration is located in exon 3 (coding exon 2) of the BDKRB2 gene. This alteration results from a G to A substitution at nucleotide position 301, causing the alanine (A) at amino acid position 101 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

.;T;.

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.16

LIST_S2

Uncertain

0.87

.;D;D

M_CAP

Benign

0.026

MetaRNN

Benign

0.099

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.3

.;M;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

-2.3

N;N;N

REVEL

Benign

0.098

Sift

Benign

0.059

T;T;T

Sift4G

Uncertain

0.058

T;T;T

Polyphen

1.0

.;D;.

Vest4

0.16

MutPred

0.38

.;Gain of glycosylation at A101 (P = 0.0531);.;

MVP

0.60

ClinPred

0.16

GERP RS

1.7

Varity_R

0.049

gMVP

0.24

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