4-78871246-G-C

Variant summary

Our verdict is Benign. Variant got -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

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 Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMP2K	NM_198892.2	c.1509+186G>C		intron_variant		ENST00000502613.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMP2K	ENST00000502613.3	c.1509+186G>C		intron_variant		1	NM_198892.2	P1
BMP2K	ENST00000502871.5	c.1509+186G>C		intron_variant		1
BMP2K	ENST00000389010.7	c.*485+186G>C		intron_variant, NMD_transcript_variant		1

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

Gnomad4 AFR AF: 0.449

Gnomad4 AMR AF: 0.0931

Gnomad4 ASJ AF: 0.0612

Gnomad4 EAS AF: 0.216

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.0576

Gnomad4 NFE AF: 0.0467

Gnomad4 OTH AF: 0.141

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.96
Dann	Benign	0.67

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

LitVar

Other links and lift over

dbSNP: rs7682144; hg19: chr4-79792400;