14-96240513-C-T

Variant names:

• chr14-96240513-C-T
• rs764968612
• NM_001379692.1:c.185C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001379692.1(BDKRB2):​c.185C>T​(p.Pro62Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,424,636 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: BDKRB2 NM_001379692.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.753

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16911218).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BDKRB2	NM_001379692.1	c.185C>T	p.Pro62Leu	missense_variant	Exon 3 of 3	ENST00000554311.2	NP_001366621.1
BDKRB2	NM_000623.4	c.185C>T	p.Pro62Leu	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.185C>T	p.Pro62Leu	missense_variant	Exon 3 of 3	1	NM_001379692.1	ENSP00000450482.1
BDKRB2	ENST00000542454.2	c.104C>T	p.Pro35Leu	missense_variant	Exon 3 of 3	1		ENSP00000439459.2
ENSG00000258691	ENST00000553811.1	c.74+3332C>T		intron_variant	Intron 2 of 3	2		ENSP00000450984.1
BDKRB2	ENST00000539359.1	c.104C>T	p.Pro35Leu	missense_variant	Exon 4 of 4	2		ENSP00000438376.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000137 AC: 3 AN: 219188 Hom.: 0 AF XY: 0.00000853 AC XY: 1 AN XY: 117218

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000298

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000112 AC: 16 AN: 1424636 Hom.: 0 Cov.: 30 AF XY: 0.0000113 AC XY: 8 AN XY: 705058

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: 0.0000146

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.59	.;D;.
Eigen	Benign	-0.052
Eigen_PC	Benign	-0.020
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.82	.;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.17	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	.;M;.
PrimateAI	Benign	0.38	T
PROVEAN	Pathogenic	-4.5	D;D;D
REVEL	Benign	0.14
Sift	Benign	0.049	D;D;D
Sift4G	Benign	0.14	T;T;T
Polyphen		0.90	.;P;.
Vest4		0.12
MutPred		0.38		.;Loss of glycosylation at P62 (P = 0.0731);.;
MVP		0.72
ClinPred		0.28	T
GERP RS		4.7
Varity_R		0.12
gMVP		0.37

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: rs764968612; hg19: chr14-96706850; COSMIC: COSV60014284; COSMIC: COSV60014284;