Variant 4-78776602-G-C 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.59G>C(p.Gly20Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000193 in 1,036,586 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000019 ( 0 hom. )

Consequence

BMP2K
NM_198892.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.21

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=0.09667027).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMP2K	NM_198892.2 linkuse as main transcript	c.59G>C	p.Gly20Ala	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.59G>C	p.Gly20Ala	missense_variant	1/16	1	NM_198892.2	ENSP00000424668	P1	Q9NSY1-1
BMP2K	ENST00000502871.5 linkuse as main transcript	c.59G>C	p.Gly20Ala	missense_variant	1/14	1		ENSP00000421768		Q9NSY1-2
BMP2K	ENST00000389010.7 linkuse as main transcript	c.59G>C	p.Gly20Ala	missense_variant, NMD_transcript_variant	1/15	1		ENSP00000373662

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000193

AC:

AN:

1036586

Hom.:

Cov.:

AF XY:

0.00000204

AC XY:

AN XY:

489086

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000225

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jul 17, 2023

The c.59G>C (p.G20A) alteration is located in exon 1 (coding exon 1) of the BMP2K gene. This alteration results from a G to C substitution at nucleotide position 59, causing the glycine (G) at amino acid position 20 to be replaced by an alanine (A). 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

Benign

0.066

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.69

DEOGEN2

Benign

0.028

.;T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.069

LIST_S2

Benign

0.48

T;T;T

M_CAP

Benign

0.074

MetaRNN

Benign

0.097

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.0

L;L;.

MutationTaster

Benign

0.64

D;D

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.72

N;N;.

REVEL

Benign

0.024

Sift

Benign

0.079

T;T;.

Sift4G

Benign

0.21

T;T;T

Polyphen

0.013

.;B;.

Vest4

0.22

MutPred

0.31

Loss of loop (P = 0.0374);Loss of loop (P = 0.0374);Loss of loop (P = 0.0374);

MVP

0.18

MPC

0.087

ClinPred

0.051

GERP RS

-0.85

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Varity_R

0.042

gMVP

0.20

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over