Genetic Variant BDKRB2:p.Lys337Arg (chr14-96241338-A-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001379692.1(BDKRB2):c.1010A>G(p.Lys337Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00209 in 1,614,064 control chromosomes in the GnomAD database, including 10 homozygotes. 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 0.0018 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0021 ( 8 hom. )

Consequence

BDKRB2
NM_001379692.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.21

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:

ENSG00000258691 (HGNC:):

ENSG00000258691 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011509657).

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BDKRB2	NM_001379692.1 link	c.1010A>G	p.Lys337Arg	missense_variant	Exon 3 of 3	ENST00000554311.2	NP_001366621.1
BDKRB2	NM_000623.4 link	c.1010A>G	p.Lys337Arg	missense_variant	Exon 3 of 3		NP_000614.1	P30411-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
BDKRB2	ENST00000554311.2 link	c.1010A>G	p.Lys337Arg	missense_variant	Exon 3 of 3	1	NM_001379692.1	ENSP00000450482.1	P30411-1
BDKRB2	ENST00000542454.2 link	c.929A>G	p.Lys310Arg	missense_variant	Exon 3 of 3	1		ENSP00000439459.2	P30411-2
ENSG00000258691	ENST00000553811.1 link	c.74+4157A>G		intron_variant	Intron 2 of 3	2		ENSP00000450984.1	G3V318
BDKRB2	ENST00000539359.1 link	c.929A>G	p.Lys310Arg	missense_variant	Exon 4 of 4	2		ENSP00000438376.1	P30411-2

Frequencies

GnomAD3 genomes

AF:

0.00177

AC:

270

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000830

Gnomad FIN

AF:

0.00489

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.00266

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00182

AC:

458

AN:

251006

Hom.:

AF XY:

0.00191

AC XY:

259

AN XY:

135662

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.000521

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000817

Gnomad FIN exome

AF:

0.00556

Gnomad NFE exome

AF:

0.00242

Gnomad OTH exome

AF:

0.00245

GnomAD4 exome

AF:

0.00212

AC:

3105

AN:

1461734

Hom.:

Cov.:

AF XY:

0.00209

AC XY:

1517

AN XY:

727176

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000537

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000951

Gnomad4 FIN exome

AF:

0.00633

Gnomad4 NFE exome

AF:

0.00229

Gnomad4 OTH exome

AF:

0.00182

GnomAD4 genome

AF:

0.00177

AC:

270

AN:

152330

Hom.:

Cov.:

AF XY:

0.00185

AC XY:

138

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.000385

Gnomad4 AMR

AF:

0.000784

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000831

Gnomad4 FIN

AF:

0.00489

Gnomad4 NFE

AF:

0.00266

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00226

Hom.:

Bravo

AF:

0.00131

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00267

AC:

ExAC

AF:

0.00166

AC:

202

EpiCase

AF:

0.00289

EpiControl

AF:

0.00190

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

.;T;.

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.88

.;D;D

M_CAP

Benign

0.0087

MetaRNN

Benign

0.012

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

.;M;.

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.5

N;N;N

REVEL

Benign

0.20

Sift

Benign

0.062

T;T;T

Sift4G

Benign

0.29

T;T;T

Polyphen

0.85

.;P;.

Vest4

0.13

MVP

0.75

ClinPred

0.029

GERP RS

4.8

Varity_R

0.18

gMVP

0.30

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