Variant rs2288255 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_198892.2(BMP2K):c.1213G>A(p.Gly405Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0485 in 1,613,836 control chromosomes in the GnomAD database, including 3,126 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.041 ( 264 hom., cov: 32)

Exomes 𝑓: 0.049 ( 2862 hom. )

Consequence

BMP2K
NM_198892.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.465

Variant links:

Genes affected

BMP2K (HGNC:18041): (BMP2 inducible kinase) This gene is the human homolog of mouse BMP-2-inducible kinase. Bone morphogenic proteins (BMPs) play a key role in skeletal development and patterning. Expression of the mouse gene is increased during BMP-2 induced differentiation and the gene product is a putative serine/threonine protein kinase containing a nuclear localization signal. Therefore, the protein encoded by this human homolog is thought to be a protein kinase with a putative regulatory role in attenuating the program of osteoblast differentiation. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

BMP2K links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0023294091).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMP2K	NM_198892.2 linkuse as main transcript	c.1213G>A	p.Gly405Ser	missense_variant	10/16	ENST00000502613.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMP2K	ENST00000502613.3 linkuse as main transcript	c.1213G>A	p.Gly405Ser	missense_variant	10/16	1	NM_198892.2	P1	Q9NSY1-1
BMP2K	ENST00000502871.5 linkuse as main transcript	c.1213G>A	p.Gly405Ser	missense_variant	10/14	1			Q9NSY1-2
BMP2K	ENST00000389010.7 linkuse as main transcript	c.*189G>A		3_prime_UTR_variant, NMD_transcript_variant	11/15	1
BMP2K	ENST00000505725.1 linkuse as main transcript	n.495G>A		non_coding_transcript_exon_variant	4/4	3

Frequencies

GnomAD3 genomes

AF:

0.0412

AC:

6259

AN:

152020

Hom.:

266

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00810

Gnomad AMI

AF:

0.00659

Gnomad AMR

AF:

0.0458

Gnomad ASJ

AF:

0.0562

Gnomad EAS

AF:

0.214

Gnomad SAS

AF:

0.104

Gnomad FIN

AF:

0.0564

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0397

Gnomad OTH

AF:

0.0459

GnomAD3 exomes

AF:

0.0609

AC:

15299

AN:

251300

Hom.:

833

AF XY:

0.0633

AC XY:

8595

AN XY:

135814

show subpopulations

Gnomad AFR exome

AF:

0.00732

Gnomad AMR exome

AF:

0.0397

Gnomad ASJ exome

AF:

0.0595

Gnomad EAS exome

AF:

0.223

Gnomad SAS exome

AF:

0.0983

Gnomad FIN exome

AF:

0.0550

Gnomad NFE exome

AF:

0.0405

Gnomad OTH exome

AF:

0.0496

GnomAD4 exome

AF:

0.0493

AC:

72046

AN:

1461698

Hom.:

2862

Cov.:

AF XY:

0.0511

AC XY:

37174

AN XY:

727184

show subpopulations

Gnomad4 AFR exome

AF:

0.00639

Gnomad4 AMR exome

AF:

0.0390

Gnomad4 ASJ exome

AF:

0.0586

Gnomad4 EAS exome

AF:

0.237

Gnomad4 SAS exome

AF:

0.0995

Gnomad4 FIN exome

AF:

0.0528

Gnomad4 NFE exome

AF:

0.0398

Gnomad4 OTH exome

AF:

0.0530

GnomAD4 genome

AF:

0.0411

AC:

6255

AN:

152138

Hom.:

264

Cov.:

AF XY:

0.0440

AC XY:

3271

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.00807

Gnomad4 AMR

AF:

0.0458

Gnomad4 ASJ

AF:

0.0562

Gnomad4 EAS

AF:

0.215

Gnomad4 SAS

AF:

0.103

Gnomad4 FIN

AF:

0.0564

Gnomad4 NFE

AF:

0.0397

Gnomad4 OTH

AF:

0.0450

Alfa

AF:

0.0461

Hom.:

370

Bravo

AF:

0.0382

TwinsUK

AF:

0.0367

AC:

136

ALSPAC

AF:

0.0371

AC:

143

ESP6500AA

AF:

0.0107

AC:

ESP6500EA

AF:

0.0392

AC:

337

ExAC

AF:

0.0609

AC:

7388

Asia WGS

AF:

0.141

AC:

487

AN:

3478

EpiCase

AF:

0.0423

EpiControl

AF:

0.0416

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.32

Cadd

Benign

7.9

Dann

Benign

0.68

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.65

T;T

MetaRNN

Benign

0.0023

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

L;L

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.95

N;N

REVEL

Benign

0.27

Sift

Benign

0.31

T;T

Sift4G

Benign

0.57

T;T

Polyphen

0.57

.;P

Vest4

0.048

MPC

0.11

ClinPred

0.0043

GERP RS

-0.26

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.7

Varity_R

0.036

gMVP

0.22

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over