NM_198892.2:c.1509+186G>C

Variant names:

• chr4-78871246-G-C
• rs7682144
• NM_198892.2:c.1509+186G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198892.2(BMP2K):​c.1509+186G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 152,092 control chromosomes in the GnomAD database, including 4,552 homozygotes. 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: 𝑓 0.17 (4552 hom., cov: 32)
• Consequence: BMP2K NM_198892.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.805
• Publications: 1 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP2K	NM_198892.2	MANE Select	c.1509+186G>C		intron	N/A	NP_942595.1
	BMP2K	NM_001419799.1		c.1509+186G>C		intron	N/A	NP_001406728.1
	BMP2K	NM_001419800.1		c.1509+186G>C		intron	N/A	NP_001406729.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP2K	ENST00000502613.3	TSL:1 MANE Select	c.1509+186G>C		intron	N/A	ENSP00000424668.2
	BMP2K	ENST00000502871.5	TSL:1	c.1509+186G>C		intron	N/A	ENSP00000421768.1
	BMP2K	ENST00000389010.7	TSL:1	n.*485+186G>C		intron	N/A	ENSP00000373662.3

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25985 AN: 151974 Hom.: 4529 Cov.: 32

Gnomad AFR AF: 0.449

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0933

Gnomad ASJ AF: 0.0612

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.0576

Gnomad MID AF: 0.0924

Gnomad NFE AF: 0.0467

Gnomad OTH AF: 0.143

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.171 AC: 26053 AN: 152092 Hom.: 4552 Cov.: 32 AF XY: 0.169 AC XY: 12568 AN XY: 74352

African (AFR) AF: 0.449 AC: 18611 AN: 41438

American (AMR) AF: 0.0931 AC: 1425 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0612 AC: 212 AN: 3466

East Asian (EAS) AF: 0.216 AC: 1119 AN: 5180

South Asian (SAS) AF: 0.118 AC: 567 AN: 4816

European-Finnish (FIN) AF: 0.0576 AC: 610 AN: 10588

Middle Eastern (MID) AF: 0.0959 AC: 28 AN: 292

European-Non Finnish (NFE) AF: 0.0467 AC: 3177 AN: 67992

Other (OTH) AF: 0.141 AC: 298 AN: 2106

Alfa AF: 0.0260 Hom.: 20

Bravo AF: 0.187

Asia WGS AF: 0.183 AC: 635 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.96
DANN	Benign	0.67
PhyloP100		-0.81
Mutation Taster		=100/0	polymorphism (auto)

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: rs7682144; hg19: chr4-79792400;