4-78851038-A-T

Position:

• chr4-78851038-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_198892.2(BMP2K):​c.865A>T​(p.Asn289Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/21 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)
• Consequence: BMP2K NM_198892.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.58

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMP2K	NM_198892.2	c.865A>T	p.Asn289Tyr	missense_variant	7/16	ENST00000502613.3	NP_942595.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMP2K	ENST00000502613.3	c.865A>T	p.Asn289Tyr	missense_variant	7/16	1	NM_198892.2	ENSP00000424668	P1
BMP2K	ENST00000502871.5	c.865A>T	p.Asn289Tyr	missense_variant	7/14	1		ENSP00000421768
BMP2K	ENST00000389010.7	c.865A>T	p.Asn289Tyr	missense_variant, NMD_transcript_variant	7/15	1		ENSP00000373662
BMP2K	ENST00000505725.1	n.147A>T		non_coding_transcript_exon_variant	1/4	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 05, 2024

The c.865A>T (p.N289Y) alteration is located in exon 7 (coding exon 7) of the BMP2K gene. This alteration results from a A to T substitution at nucleotide position 865, causing the asparagine (N) at amino acid position 289 to be replaced by a tyrosine (Y). 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	0.13
BayesDel_addAF	Benign	-0.078	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.060	.;T;.
Eigen	Benign	-0.033
Eigen_PC	Benign	-0.093
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Benign	0.050	D
MetaRNN	Uncertain	0.43	T;T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.1	L;L;.
MutationTaster	Benign	0.95	N;N
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-3.9	D;D;.
REVEL	Benign	0.20
Sift	Uncertain	0.028	D;D;.
Sift4G	Uncertain	0.016	D;D;T
Polyphen		0.95	.;P;.
Vest4		0.40
MutPred		0.57		Gain of glycosylation at S287 (P = 0.0844);Gain of glycosylation at S287 (P = 0.0844);Gain of glycosylation at S287 (P = 0.0844);
MVP		0.66
MPC		0.46
ClinPred		0.95	D
GERP RS		1.6
Varity_R		0.34
gMVP		0.64

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.

Other links and lift over

hg19: chr4-79772192;