14-96240563-C-T

Variant names:

• chr14-96240563-C-T
• rs1885250697
• NM_001379692.1:c.235C>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001379692.1(BDKRB2):​c.235C>T​(p.Leu79Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000914 in 1,421,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L79V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000091 (0 hom.)
• Consequence: BDKRB2 NM_001379692.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.80
• Publications: 0 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.854

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.235C>T	p.Leu79Phe	missense	Exon 3 of 3	NP_001366621.1	P30411-1
	BDKRB2	NM_000623.4		c.235C>T	p.Leu79Phe	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.235C>T	p.Leu79Phe	missense	Exon 3 of 3	ENSP00000450482.1	P30411-1
	BDKRB2	ENST00000542454.2	TSL:1	c.154C>T	p.Leu52Phe	missense	Exon 3 of 3	ENSP00000439459.2	P30411-2
	ENSG00000258691	ENST00000553811.1	TSL:2	c.74+3382C>T		intron	N/A	ENSP00000450984.1	G3V318

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000914 AC: 13 AN: 1421836 Hom.: 0 Cov.: 30 AF XY: 0.00000995 AC XY: 7 AN XY: 703176

African (AFR) AF: 0.00 AC: 0 AN: 32298

American (AMR) AF: 0.00 AC: 0 AN: 38988

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23260

East Asian (EAS) AF: 0.00 AC: 0 AN: 39434

South Asian (SAS) AF: 0.00 AC: 0 AN: 78648

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51786

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5560

European-Non Finnish (NFE) AF: 0.0000110 AC: 12 AN: 1093140

Other (OTH) AF: 0.0000170 AC: 1 AN: 58722

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.62	D
Eigen	Pathogenic	0.72
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.88	D
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.85	D
MetaSVM	Uncertain	0.33	D
MutationAssessor	Uncertain	2.9	M
PhyloP100		4.8
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-3.8	D
REVEL	Uncertain	0.64
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.77
MutPred		0.54		Gain of sheet (P = 0.1451)
MVP		0.93
ClinPred		1.0	D
GERP RS		4.7
Varity_R		0.79
gMVP		0.64
Mutation Taster		=52/48	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: rs1885250697; hg19: chr14-96706900;