14-96240949-C-G

Variant names:

• chr14-96240949-C-G
• rs200470118
• NM_001379692.1:c.621C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001379692.1(BDKRB2):​c.621C>G​(p.Asn207Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,174 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 (0 hom., cov: 32)
• Consequence: BDKRB2 NM_001379692.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.614

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]

ENSG00000258691 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32455343).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BDKRB2	NM_001379692.1	c.621C>G	p.Asn207Lys	missense_variant	Exon 3 of 3	ENST00000554311.2	NP_001366621.1
BDKRB2	NM_000623.4	c.621C>G	p.Asn207Lys	missense_variant	Exon 3 of 3		NP_000614.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BDKRB2	ENST00000554311.2	c.621C>G	p.Asn207Lys	missense_variant	Exon 3 of 3	1	NM_001379692.1	ENSP00000450482.1
BDKRB2	ENST00000542454.2	c.540C>G	p.Asn180Lys	missense_variant	Exon 3 of 3	1		ENSP00000439459.2
ENSG00000258691	ENST00000553811.1	c.74+3768C>G		intron_variant	Intron 2 of 3	2		ENSP00000450984.1
BDKRB2	ENST00000539359.1	c.540C>G	p.Asn180Lys	missense_variant	Exon 4 of 4	2		ENSP00000438376.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152174 Hom.: 0 Cov.: 32

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

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152174 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74334

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.59	.;D;.
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.77	.;T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.32	T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.4	.;M;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-3.6	D;D;D
REVEL	Benign	0.14
Sift	Uncertain	0.0060	D;D;D
Sift4G	Benign	0.078	T;T;T
Polyphen		1.0	.;D;.
Vest4		0.18
MutPred		0.62		.;Gain of methylation at N207 (P = 0.0055);.;
MVP		0.69
ClinPred		0.98	D
GERP RS		-0.56
Varity_R		0.26
gMVP		0.58

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

Other links and lift over

dbSNP: rs200470118; hg19: chr14-96707286;