dbSNP rs777127820: BMP2K:p.Ala231Thr (chr4-78847210-G-A) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_198892.2(BMP2K):c.691G>A(p.Ala231Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

BMP2K
NM_198892.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.59

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 Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.956

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP2K	NM_198892.2 link	c.691G>A	p.Ala231Thr	missense_variant	Exon 6 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.691G>A	p.Ala231Thr	missense_variant	Exon 6 of 16	1	NM_198892.2	ENSP00000424668.2	Q9NSY1-1H0Y9P1
BMP2K	ENST00000502871.5 link	c.691G>A	p.Ala231Thr	missense_variant	Exon 6 of 14	1		ENSP00000421768.1	Q9NSY1-2
BMP2K	ENST00000389010.7 link	n.691G>A		non_coding_transcript_exon_variant	Exon 6 of 15	1		ENSP00000373662.3	K4DI97

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000835

AC:

AN:

239430

Hom.:

AF XY:

0.00000767

AC XY:

AN XY:

130368

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000182

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1431644

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

712812

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000255

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.74

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Uncertain

0.10

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.14

.;T;.

Eigen

Pathogenic

0.82

Eigen_PC

Pathogenic

0.73

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.94

D;D;D

M_CAP

Benign

0.050

MetaRNN

Pathogenic

0.96

D;D;D

MetaSVM

Uncertain

-0.074

MutationAssessor

Pathogenic

3.7

H;H;.

PrimateAI

Uncertain

0.75

PROVEAN

Uncertain

-3.6

D;D;.

REVEL

Uncertain

0.51

Sift

Benign

0.050

D;D;.

Sift4G

Uncertain

0.0040

D;D;D

Polyphen

1.0

.;D;.

Vest4

0.94

MutPred

0.89

Gain of glycosylation at Y229 (P = 0.1789);Gain of glycosylation at Y229 (P = 0.1789);Gain of glycosylation at Y229 (P = 0.1789);

MVP

0.56

MPC

0.44

ClinPred

0.98

GERP RS

4.5

Varity_R

0.50

gMVP

0.86

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over