Variant 4-78776562-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_198892.2(BMP2K):c.19A>G(p.Met7Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000262 in 1,145,252 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000010 ( 0 hom. )

Consequence

BMP2K
NM_198892.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.18

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 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=0.2611032).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMP2K	NM_198892.2 linkuse as main transcript	c.19A>G	p.Met7Val	missense_variant	1/16	ENST00000502613.3	NP_942595.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMP2K	ENST00000502613.3 linkuse as main transcript	c.19A>G	p.Met7Val	missense_variant	1/16	1	NM_198892.2	ENSP00000424668	P1	Q9NSY1-1
BMP2K	ENST00000502871.5 linkuse as main transcript	c.19A>G	p.Met7Val	missense_variant	1/14	1		ENSP00000421768		Q9NSY1-2
BMP2K	ENST00000389010.7 linkuse as main transcript	c.19A>G	p.Met7Val	missense_variant, NMD_transcript_variant	1/15	1		ENSP00000373662

Frequencies

GnomAD3 genomes

AF:

0.0000134

AC:

AN:

149716

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000396

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000100

AC:

AN:

995430

Hom.:

Cov.:

AF XY:

0.00000213

AC XY:

AN XY:

468446

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000610

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000133

AC:

AN:

149822

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73168

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000397

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 17, 2024

The c.19A>G (p.M7V) alteration is located in exon 1 (coding exon 1) of the BMP2K gene. This alteration results from a A to G substitution at nucleotide position 19, causing the methionine (M) at amino acid position 7 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.49

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.030

CADD

Benign

DANN

Benign

0.83

DEOGEN2

Benign

0.027

.;T;.

Eigen

Benign

-0.081

Eigen_PC

Benign

-0.083

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.68

T;T;T

M_CAP

Pathogenic

0.79

MetaRNN

Benign

0.26

T;T;T

MetaSVM

Benign

-0.75

MutationAssessor

Benign

1.5

L;L;.

MutationTaster

Benign

0.98

D;D

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-1.0

N;N;.

REVEL

Benign

0.26

Sift

Pathogenic

0.0

D;D;.

Sift4G

Benign

0.22

T;T;T

Polyphen

0.92

.;P;.

Vest4

0.49

MutPred

0.30

Gain of glycosylation at S5 (P = 0.0103);Gain of glycosylation at S5 (P = 0.0103);Gain of glycosylation at S5 (P = 0.0103);

MVP

0.57

MPC

0.084

ClinPred

0.54

GERP RS

3.6

Varity_R

0.87

gMVP

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over