chr14-96240954-C-A

Variant names:

• chr14-96240954-C-A
• rs200062156
• NM_001379692.1:c.626C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001379692.1(BDKRB2):​c.626C>A​(p.Thr209Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000879 in 1,592,454 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000088 (0 hom.)
• Consequence: BDKRB2 NM_001379692.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.94
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001379692.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BDKRB2	NM_001379692.1	MANE Select	c.626C>A	p.Thr209Asn	missense	Exon 3 of 3	NP_001366621.1	P30411-1
	BDKRB2	NM_000623.4		c.626C>A	p.Thr209Asn	missense	Exon 3 of 3	NP_000614.1	P30411-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BDKRB2	ENST00000554311.2	TSL:1 MANE Select	c.626C>A	p.Thr209Asn	missense	Exon 3 of 3	ENSP00000450482.1	P30411-1
	BDKRB2	ENST00000542454.2	TSL:1	c.545C>A	p.Thr182Asn	missense	Exon 3 of 3	ENSP00000439459.2	P30411-2
	ENSG00000258691	ENST00000553811.1	TSL:2	c.74+3773C>A		intron	N/A	ENSP00000450984.1	G3V318

Frequencies

GnomAD3 genomes AF: 0.0000854 AC: 13 AN: 152186 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: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000906 AC: 21 AN: 231708 AF XY: 0.0000808

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 FIN exome AF: 0.0000492

Gnomad NFE exome AF: 0.000182

Gnomad OTH exome AF: 0.000178

GnomAD4 exome AF: 0.0000882 AC: 127 AN: 1440268 Hom.: 0 Cov.: 30 AF XY: 0.0000953 AC XY: 68 AN XY: 713566

African (AFR) AF: 0.00 AC: 0 AN: 33232

American (AMR) AF: 0.00 AC: 0 AN: 43612

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24484

East Asian (EAS) AF: 0.00 AC: 0 AN: 39510

South Asian (SAS) AF: 0.00 AC: 0 AN: 81804

European-Finnish (FIN) AF: 0.000114 AC: 6 AN: 52470

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5672

European-Non Finnish (NFE) AF: 0.000108 AC: 119 AN: 1100070

Other (OTH) AF: 0.0000337 AC: 2 AN: 59414

GnomAD4 genome AF: 0.0000854 AC: 13 AN: 152186 Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9 AN XY: 74346

African (AFR) AF: 0.0000241 AC: 1 AN: 41450

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000132 Hom.: 0

Bravo AF: 0.0000642

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000107 AC: 13

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.33	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.025	T
MetaRNN	Uncertain	0.64	D
MetaSVM	Benign	-0.77	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		2.9
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.24
Sift	Uncertain	0.019	D
Sift4G	Uncertain	0.052	T
Polyphen		0.99	D
Vest4		0.56
MVP		0.91
ClinPred		0.41	T
GERP RS		4.1
Varity_R		0.20
gMVP		0.76
Mutation Taster		=75/25	polymorphism

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

Other links and lift over

dbSNP: rs200062156; hg19: chr14-96707291;