Variant chr4-78776587-G-A 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.44G>A(p.Gly15Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000128 in 1,167,826 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 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

BMP2K
NM_198892.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.39

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=0.15257004).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMP2K	NM_198892.2 linkuse as main transcript	c.44G>A	p.Gly15Asp	missense_variant	1/16	ENST00000502613.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMP2K	ENST00000502613.3 linkuse as main transcript	c.44G>A	p.Gly15Asp	missense_variant	1/16	1	NM_198892.2	P1	Q9NSY1-1
BMP2K	ENST00000502871.5 linkuse as main transcript	c.44G>A	p.Gly15Asp	missense_variant	1/14	1			Q9NSY1-2
BMP2K	ENST00000389010.7 linkuse as main transcript	c.44G>A	p.Gly15Asp	missense_variant, NMD_transcript_variant	1/15	1

Frequencies

GnomAD3 genomes

AF:

0.0000200

AC:

AN:

150312

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000297

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000118

AC:

AN:

1017514

Hom.:

Cov.:

AF XY:

0.0000125

AC XY:

AN XY:

479494

show subpopulations

Gnomad4 AFR exome

AF:

0.0000491

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:

0.0000126

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000200

AC:

AN:

150312

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73324

show subpopulations

Gnomad4 AFR

AF:

0.0000243

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000297

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000843

Hom.:

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 15, 2024

The c.44G>A (p.G15D) alteration is located in exon 1 (coding exon 1) of the BMP2K gene. This alteration results from a G to A substitution at nucleotide position 44, causing the glycine (G) at amino acid position 15 to be replaced by an aspartic acid (D). 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

0.51

BayesDel_addAF

Benign

-0.0028

BayesDel_noAF

Benign

-0.24

CADD

Pathogenic

DANN

Uncertain

0.97

DEOGEN2

Benign

0.043

.;T;.

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.57

T;T;T

M_CAP

Benign

0.020

MetaRNN

Benign

0.15

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

M;M;.

MutationTaster

Benign

0.92

N;N

PrimateAI

Pathogenic

0.91

PROVEAN

Uncertain

-2.6

D;N;.

REVEL

Benign

0.049

Sift

Uncertain

0.0030

D;D;.

Sift4G

Uncertain

0.043

D;D;D

Polyphen

0.0010

.;B;.

Vest4

0.27

MutPred

0.35

Gain of glycosylation at S10 (P = 0.0397);Gain of glycosylation at S10 (P = 0.0397);Gain of glycosylation at S10 (P = 0.0397);

MVP

0.33

MPC

0.24

ClinPred

0.55

GERP RS

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.4

Varity_R

0.33

gMVP

0.25

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over