Variant 14-96240794-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001379692.1(BDKRB2):c.466T>C(p.Tyr156His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,401,560 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

BDKRB2
NM_001379692.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.92

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 Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.983

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BDKRB2	NM_001379692.1 linkuse as main transcript	c.466T>C	p.Tyr156His	missense_variant	3/3	ENST00000554311.2	NP_001366621.1
BDKRB2	NM_000623.4 linkuse as main transcript	c.466T>C	p.Tyr156His	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.466T>C	p.Tyr156His	missense_variant	3/3	1	NM_001379692.1	ENSP00000450482.1	P30411-1
BDKRB2	ENST00000542454.2 linkuse as main transcript	c.385T>C	p.Tyr129His	missense_variant	3/3	1		ENSP00000439459.2	P30411-2
ENSG00000258691	ENST00000553811.1 linkuse as main transcript	c.74+3613T>C		intron_variant		2		ENSP00000450984.1	G3V318
BDKRB2	ENST00000539359.1 linkuse as main transcript	c.385T>C	p.Tyr129His	missense_variant	4/4	2		ENSP00000438376.1	P30411-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000143

AC:

AN:

1401560

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

690646

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:

0.00

Gnomad4 NFE exome

AF:

0.00000185

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Apr 07, 2022

The c.466T>C (p.Y156H) alteration is located in exon 3 (coding exon 2) of the BDKRB2 gene. This alteration results from a T to C substitution at nucleotide position 466, causing the tyrosine (Y) at amino acid position 156 to be replaced by a histidine (H). 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

Pathogenic

0.82

BayesDel_addAF

Pathogenic

0.39

BayesDel_noAF

Pathogenic

0.33

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.74

.;D;.

Eigen

Pathogenic

0.87

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.90

.;D;D

M_CAP

Uncertain

0.12

MetaRNN

Pathogenic

0.98

D;D;D

MetaSVM

Pathogenic

0.90

MutationAssessor

Pathogenic

4.3

.;H;.

PrimateAI

Pathogenic

0.80

PROVEAN

Pathogenic

-5.0

D;D;D

REVEL

Pathogenic

0.95

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

.;D;.

Vest4

0.91

MutPred

0.92

.;Loss of stability (P = 0.0361);.;

MVP

0.92

ClinPred

1.0

GERP RS

4.9

Varity_R

0.87

gMVP

0.85

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over