chr4-78842424-C-A

Variant names:

• chr4-78842424-C-A
• rs200170520
• NM_198892.2:c.443C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_198892.2(BMP2K):​c.443C>A​(p.Thr148Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T148M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BMP2K NM_198892.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.12
• Publications: 2 publications found

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]

ACMG classification

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=0.2476038).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP2K	NM_198892.2	MANE Select	c.443C>A	p.Thr148Lys	missense	Exon 4 of 16	NP_942595.1	Q9NSY1-1
	BMP2K	NM_001419799.1		c.443C>A	p.Thr148Lys	missense	Exon 4 of 15	NP_001406728.1
	BMP2K	NM_001419800.1		c.443C>A	p.Thr148Lys	missense	Exon 4 of 16	NP_001406729.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP2K	ENST00000502613.3	TSL:1 MANE Select	c.443C>A	p.Thr148Lys	missense	Exon 4 of 16	ENSP00000424668.2	Q9NSY1-1
	BMP2K	ENST00000502871.5	TSL:1	c.443C>A	p.Thr148Lys	missense	Exon 4 of 14	ENSP00000421768.1	Q9NSY1-2
	BMP2K	ENST00000389010.7	TSL:1	n.443C>A		non_coding_transcript_exon	Exon 4 of 15	ENSP00000373662.3	K4DI97

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.017	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.065	T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.054	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.53	T
MutationAssessor	Benign	-0.59	N
PhyloP100		3.1
PrimateAI	Uncertain	0.61	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Benign	0.19
Sift	Benign	0.094	T
Sift4G	Uncertain	0.0090	D
Polyphen		0.94	P
Vest4		0.44
MutPred		0.37		Gain of methylation at T148 (P = 0.023)
MVP		0.71
MPC		0.43
ClinPred		0.95	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.58
gMVP		0.37
Mutation Taster		=81/19	polymorphism

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

Other links and lift over

dbSNP: rs200170520; hg19: chr4-79763578;