Genetic Variant BDKRB2:p.Thr209Ile (chr14-96240954-C-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001379692.1(BDKRB2):c.626C>T(p.Thr209Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000377 in 1,592,454 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

BDKRB2
NM_001379692.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.94

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.779

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BDKRB2	NM_001379692.1 link	c.626C>T	p.Thr209Ile	missense_variant	Exon 3 of 3	ENST00000554311.2	NP_001366621.1
BDKRB2	NM_000623.4 link	c.626C>T	p.Thr209Ile	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.626C>T	p.Thr209Ile	missense_variant	Exon 3 of 3	1	NM_001379692.1	ENSP00000450482.1	P30411-1
BDKRB2	ENST00000542454.2 link	c.545C>T	p.Thr182Ile	missense_variant	Exon 3 of 3	1		ENSP00000439459.2	P30411-2
ENSG00000258691	ENST00000553811.1 link	c.74+3773C>T		intron_variant	Intron 2 of 3	2		ENSP00000450984.1	G3V318
BDKRB2	ENST00000539359.1 link	c.545C>T	p.Thr182Ile	missense_variant	Exon 4 of 4	2		ENSP00000438376.1	P30411-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000129

AC:

AN:

231708

Hom.:

AF XY:

0.00000808

AC XY:

AN XY:

123750

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000147

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000347

AC:

AN:

1440268

Hom.:

Cov.:

AF XY:

0.00000280

AC XY:

AN XY:

713566

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000953

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000165

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Uncertain

0.024

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.59

.;D;.

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.74

.;T;T

M_CAP

Benign

0.029

MetaRNN

Pathogenic

0.78

D;D;D

MetaSVM

Benign

-0.74

MutationAssessor

Benign

2.0

.;M;.

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-3.6

D;D;D

REVEL

Benign

0.25

Sift

Uncertain

0.0060

D;D;D

Sift4G

Benign

0.064

T;T;T

Polyphen

0.97

.;D;.

Vest4

0.63

MutPred

0.71

.;Loss of disorder (P = 0.0513);.;

MVP

0.91

ClinPred

0.68

GERP RS

4.1

Varity_R

0.24

gMVP

0.72

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