Variant 14-96240548-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001379692.1(BDKRB2):c.220G>C(p.Glu74Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000019 in 1,582,458 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

BDKRB2
NM_001379692.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.17

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BDKRB2	NM_001379692.1 linkuse as main transcript	c.220G>C	p.Glu74Gln	missense_variant	3/3	ENST00000554311.2	NP_001366621.1
BDKRB2	NM_000623.4 linkuse as main transcript	c.220G>C	p.Glu74Gln	missense_variant	3/3		NP_000614.1	P30411-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
BDKRB2	ENST00000554311.2 linkuse as main transcript	c.220G>C	p.Glu74Gln	missense_variant	3/3	1	NM_001379692.1	ENSP00000450482.1	P30411-1
BDKRB2	ENST00000542454.2 linkuse as main transcript	c.139G>C	p.Glu47Gln	missense_variant	3/3	1		ENSP00000439459.2	P30411-2
ENSG00000258691	ENST00000553811.1 linkuse as main transcript	c.74+3367G>C		intron_variant		2		ENSP00000450984.1	G3V318
BDKRB2	ENST00000539359.1 linkuse as main transcript	c.139G>C	p.Glu47Gln	missense_variant	4/4	2		ENSP00000438376.1	P30411-2

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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:

0.00000451

AC:

AN:

221866

Hom.:

AF XY:

0.00000843

AC XY:

AN XY:

118686

show subpopulations

Gnomad AFR exome

AF:

0.0000630

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:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.99e-7

AC:

AN:

1430398

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

708482

show subpopulations

Gnomad4 AFR exome

AF:

0.0000306

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:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152060

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74278

show subpopulations

Gnomad4 AFR

AF:

0.0000483

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

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

Dec 03, 2024

The c.220G>C (p.E74Q) alteration is located in exon 3 (coding exon 2) of the BDKRB2 gene. This alteration results from a G to C substitution at nucleotide position 220, causing the glutamic acid (E) at amino acid position 74 to be replaced by a glutamine (Q). 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

0.30

BayesDel_addAF

Benign

-0.026

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.43

.;T;.

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.84

.;T;T

M_CAP

Benign

0.017

MetaRNN

Uncertain

0.54

D;D;D

MetaSVM

Benign

-0.75

MutationAssessor

Benign

1.9

.;L;.

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.83

N;N;N

REVEL

Benign

0.24

Sift

Benign

0.29

T;T;T

Sift4G

Benign

0.32

T;T;T

Polyphen

1.0

.;D;.

Vest4

0.38

MutPred

0.73

.;Loss of sheet (P = 0.302);.;

MVP

0.88

ClinPred

0.51

GERP RS

4.7

Varity_R

0.15

gMVP

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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