14-96241389-G-A

Position:

• chr14-96241389-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000554311.2(BDKRB2):​c.1061G>A​(p.Gly354Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00347 in 1,612,930 control chromosomes in the GnomAD database, including 140 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Synonymous variant affecting the same amino acid position (i.e. G354G) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.016 (65 hom., cov: 33)
  • Exomes 𝑓: 0.0021 (75 hom.)
• Consequence: BDKRB2 ENST00000554311.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.162

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0019967258).
• BP6: Variant 14-96241389-G-A is Benign according to our data. Variant chr14-96241389-G-A is described in ClinVar as [Benign]. Clinvar id is 787954.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BDKRB2	NM_001379692.1	c.1061G>A	p.Gly354Glu	missense_variant	3/3	ENST00000554311.2	NP_001366621.1
BDKRB2	NM_000623.4	c.1061G>A	p.Gly354Glu	missense_variant	3/3		NP_000614.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BDKRB2	ENST00000554311.2	c.1061G>A	p.Gly354Glu	missense_variant	3/3	1	NM_001379692.1	ENSP00000450482	P1
BDKRB2	ENST00000542454.2	c.980G>A	p.Gly327Glu	missense_variant	3/3	1		ENSP00000439459
BDKRB2	ENST00000539359.1	c.980G>A	p.Gly327Glu	missense_variant	4/4	2		ENSP00000438376

Frequencies

GnomAD3 genomes AF: 0.0163 AC: 2485 AN: 152144 Hom.: 64 Cov.: 33

Gnomad AFR AF: 0.0550

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00818

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000830

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000647

Gnomad OTH AF: 0.0158

GnomAD3 exomes AF: 0.00497 AC: 1240 AN: 249742 Hom.: 38 AF XY: 0.00369 AC XY: 498 AN XY: 135026

Gnomad AFR exome AF: 0.0594

Gnomad AMR exome AF: 0.00515

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000392

Gnomad FIN exome AF: 0.0000979

Gnomad NFE exome AF: 0.000512

Gnomad OTH exome AF: 0.00409

GnomAD4 exome AF: 0.00212 AC: 3094 AN: 1460668 Hom.: 75 Cov.: 33 AF XY: 0.00187 AC XY: 1357 AN XY: 726644

Gnomad4 AFR exome AF: 0.0593

Gnomad4 AMR exome AF: 0.00541

Gnomad4 ASJ exome AF: 0.000191

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000359

Gnomad4 FIN exome AF: 0.000134

Gnomad4 NFE exome AF: 0.000423

Gnomad4 OTH exome AF: 0.00538

GnomAD4 genome AF: 0.0164 AC: 2496 AN: 152262 Hom.: 65 Cov.: 33 AF XY: 0.0157 AC XY: 1167 AN XY: 74444

Gnomad4 AFR AF: 0.0551

Gnomad4 AMR AF: 0.00817

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000831

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000647

Gnomad4 OTH AF: 0.0156

Alfa AF: 0.00327 Hom.: 19

Bravo AF: 0.0186

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00104 AC: 4

ESP6500AA AF: 0.0529 AC: 233

ESP6500EA AF: 0.000581 AC: 5

ExAC AF: 0.00588 AC: 714

Asia WGS AF: 0.00433 AC: 16 AN: 3478

EpiCase AF: 0.000654

EpiControl AF: 0.000533

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 16, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	9.6
DANN	Benign	0.80
DEOGEN2	Benign	0.16	.;T;.
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.44	.;T;T
MetaRNN	Benign	0.0020	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	.;L;.
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.58	N;N;N
REVEL	Benign	0.035
Sift	Benign	0.49	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.017	.;B;.
Vest4		0.058
MVP		0.59
ClinPred		0.0058	T
GERP RS		-1.0
Varity_R		0.036
gMVP		0.24

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: rs2227279; hg19: chr14-96707726;