NM_198892.2:c.98G>A

Variant names:

• chr4-78776641-G-A
• NM_198892.2:c.98G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_198892.2(BMP2K):​c.98G>A​(p.Gly33Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000187 in 1,068,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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: 0.0000019 (0 hom.)
• Consequence: BMP2K NM_198892.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.03

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17795286).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP2K	NM_198892.2	c.98G>A	p.Gly33Asp	missense_variant	Exon 1 of 16	ENST00000502613.3	NP_942595.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMP2K	ENST00000502613.3	c.98G>A	p.Gly33Asp	missense_variant	Exon 1 of 16	1	NM_198892.2	ENSP00000424668.2
BMP2K	ENST00000502871.5	c.98G>A	p.Gly33Asp	missense_variant	Exon 1 of 14	1		ENSP00000421768.1
BMP2K	ENST00000389010.7	n.98G>A		non_coding_transcript_exon_variant	Exon 1 of 15	1		ENSP00000373662.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000187 AC: 2 AN: 1068840 Hom.: 0 Cov.: 31 AF XY: 0.00000396 AC XY: 2 AN XY: 504784

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.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Benign	-0.014	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.038	.;T;.
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.42	T;T;T
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L;L;.
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-1.9	N;N;.
REVEL	Benign	0.093
Sift	Benign	0.12	T;T;.
Sift4G	Benign	0.11	T;D;T
Polyphen		0.62	.;P;.
Vest4		0.22
MutPred		0.34		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		0.35
MPC		0.49
ClinPred		0.83	D
GERP RS		2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.4
Varity_R		0.10
gMVP		0.32

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: chr4-79697795;