14-96240871-C-G

Position:

• chr14-96240871-C-G

Variant summary

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

The ENST00000554311.2(BDKRB2):​c.543C>G​(p.Ile181Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BDKRB2 ENST00000554311.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0770

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]

ACMG classification

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	c.543C>G	p.Ile181Met	missense_variant	3/3	ENST00000554311.2	NP_001366621.1
BDKRB2	NM_000623.4	c.543C>G	p.Ile181Met	missense_variant	3/3		NP_000614.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BDKRB2	ENST00000554311.2	c.543C>G	p.Ile181Met	missense_variant	3/3	1	NM_001379692.1	ENSP00000450482	P1
BDKRB2	ENST00000542454.2	c.462C>G	p.Ile154Met	missense_variant	3/3	1		ENSP00000439459
BDKRB2	ENST00000539359.1	c.462C>G	p.Ile154Met	missense_variant	4/4	2		ENSP00000438376

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 28, 2024

The c.543C>G (p.I181M) alteration is located in exon 3 (coding exon 2) of the BDKRB2 gene. This alteration results from a C to G substitution at nucleotide position 543, causing the isoleucine (I) at amino acid position 181 to be replaced by a methionine (M). 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	0.23
BayesDel_addAF	Benign	-0.036	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.44	.;T;.
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.66	.;T;T
M_CAP	Benign	0.048	D
MetaRNN	Uncertain	0.46	T;T;T
MetaSVM	Uncertain	-0.24	T
MutationAssessor	Uncertain	2.7	.;M;.
MutationTaster	Benign	0.95	D;D;D;D
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-2.0	N;N;N
REVEL	Uncertain	0.46
Sift	Benign	0.044	D;D;D
Sift4G	Benign	0.086	T;T;T
Polyphen		0.97	.;D;.
Vest4		0.27
MutPred		0.71		.;Gain of MoRF binding (P = 0.0708);.;
MVP		0.85
ClinPred		0.74	D
GERP RS		1.6
Varity_R		0.13
gMVP		0.75

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.

Other links and lift over

hg19: chr14-96707208;