Genetic Variant BMP2K:p.Ser34Phe (chr4-78776644-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_198892.2(BMP2K):c.101C>T(p.Ser34Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000164 in 1,221,538 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 9.3e-7 ( 0 hom. )

Consequence

BMP2K
NM_198892.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.177

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.070094705).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198892.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BMP2K	NM_198892.2	MANE Select	c.101C>T	p.Ser34Phe	missense	Exon 1 of 16	NP_942595.1	Q9NSY1-1
BMP2K	NM_001419799.1		c.101C>T	p.Ser34Phe	missense	Exon 1 of 15	NP_001406728.1
BMP2K	NM_001419800.1		c.101C>T	p.Ser34Phe	missense	Exon 1 of 16	NP_001406729.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BMP2K	ENST00000502613.3	TSL:1 MANE Select	c.101C>T	p.Ser34Phe	missense	Exon 1 of 16	ENSP00000424668.2	Q9NSY1-1
BMP2K	ENST00000502871.5	TSL:1	c.101C>T	p.Ser34Phe	missense	Exon 1 of 14	ENSP00000421768.1	Q9NSY1-2
BMP2K	ENST00000389010.7	TSL:1	n.101C>T		non_coding_transcript_exon	Exon 1 of 15	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:

0.000194

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:

9.34e-7

AC:

AN:

1070864

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

505776

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22338

American (AMR)

AF:

0.00

AC:

AN:

7910

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13536

East Asian (EAS)

AF:

0.0000393

AC:

AN:

25464

South Asian (SAS)

AF:

0.00

AC:

AN:

19466

European-Finnish (FIN)

AF:

0.00

AC:

AN:

26766

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2830

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

910106

Other (OTH)

AF:

0.00

AC:

AN:

42448

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000664

AC:

AN:

150674

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73516

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41270

American (AMR)

AF:

0.00

AC:

AN:

15152

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3432

East Asian (EAS)

AF:

0.000194

AC:

AN:

5154

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10148

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67412

Other (OTH)

AF:

0.00

AC:

AN:

2060

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.030

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.0069

LIST_S2

Benign

0.46

M_CAP

Benign

0.024

MetaRNN

Benign

0.070

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

PhyloP100

0.18

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

0.56

REVEL

Benign

0.035

Sift

Benign

0.70

Sift4G

Benign

0.70

Polyphen

0.0010

Vest4

0.11

MutPred

0.31

Loss of glycosylation at S38 (P = 0.0608)

MVP

0.24

MPC

0.088

ClinPred

0.10

GERP RS

2.8

PromoterAI

0.024

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.4

Varity_R

0.044

gMVP

0.27

Mutation Taster

=88/12

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over