dbSNP rs1727255973: BMP2K:p.Ser34Cys (chr4-78776644-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_198892.2(BMP2K):c.101C>G(p.Ser34Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000664 in 150,674 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

BMP2K
NM_198892.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.177

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=0.13247809).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP2K	NM_198892.2 link	c.101C>G	p.Ser34Cys	missense_variant	Exon 1 of 16	ENST00000502613.3	NP_942595.1	Q9NSY1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
BMP2K	ENST00000502613.3 link	c.101C>G	p.Ser34Cys	missense_variant	Exon 1 of 16	1	NM_198892.2	ENSP00000424668.2	Q9NSY1-1H0Y9P1
BMP2K	ENST00000502871.5 link	c.101C>G	p.Ser34Cys	missense_variant	Exon 1 of 14	1		ENSP00000421768.1	Q9NSY1-2
BMP2K	ENST00000389010.7 link	n.101C>G		non_coding_transcript_exon_variant	Exon 1 of 15	1		ENSP00000373662.3	K4DI97

Frequencies

GnomAD3 genomes

AF:

0.00000664

AC:

AN:

150674

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000664

AC:

AN:

150674

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73516

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000148

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.039

.;T;.

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.32

T;T;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.13

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

L;L;.

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.92

N;N;.

REVEL

Benign

0.022

Sift

Benign

0.14

T;T;.

Sift4G

Benign

0.18

T;T;T

Polyphen

0.79

.;P;.

Vest4

0.13

MutPred

0.31

Loss of glycosylation at S38 (P = 0.0608);Loss of glycosylation at S38 (P = 0.0608);Loss of glycosylation at S38 (P = 0.0608);

MVP

0.24

MPC

0.20

ClinPred

0.23

GERP RS

2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.4

Varity_R

0.083

gMVP

0.33

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