Variant rs138262352 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_198892.2(BMP2K):c.3481C>G(p.Gln1161Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000777 in 1,601,244 control chromosomes in the GnomAD database, including 2 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 0.00056 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00080 ( 2 hom. )

Consequence

BMP2K
NM_198892.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.20

Variant links:

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]

BMP2K links:

PAQR3 (HGNC:30130): (progestin and adipoQ receptor family member 3) This gene encodes a seven-transmembrane protein localized in the Golgi apparatus in mammalian cells. The encoded protein belongs to the progestin and adipoQ receptor (PAQR) family. This protein functions as a tumor suppressor by inhibiting the Raf/MEK/ERK signaling cascade. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2017]

PAQR3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.05437389).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP2K	NM_198892.2 link	c.3481C>G	p.Gln1161Glu	missense_variant	Exon 16 of 16	ENST00000502613.3	NP_942595.1	Q9NSY1-1
PAQR3	NM_001040202.2 link	c.*8511G>C		3_prime_UTR_variant	Exon 6 of 6	ENST00000512733.5	NP_001035292.1	Q6TCH7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMP2K	ENST00000502613.3 link	c.3481C>G	p.Gln1161Glu	missense_variant	Exon 16 of 16	1	NM_198892.2	ENSP00000424668.2		Q9NSY1-1H0Y9P1
PAQR3	ENST00000512733 link	c.*8511G>C		3_prime_UTR_variant	Exon 6 of 6	1	NM_001040202.2	ENSP00000421981.1		Q6TCH7-1

Frequencies

GnomAD3 genomes

AF:

0.000559

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000982

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000926

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000681

AC:

163

AN:

239366

Hom.:

AF XY:

0.000710

AC XY:

AN XY:

129494

show subpopulations

Gnomad AFR exome

AF:

0.0000651

Gnomad AMR exome

AF:

0.000846

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000281

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00109

Gnomad OTH exome

AF:

0.00121

GnomAD4 exome

AF:

0.000800

AC:

1159

AN:

1448934

Hom.:

Cov.:

AF XY:

0.000765

AC XY:

550

AN XY:

719336

show subpopulations

Gnomad4 AFR exome

AF:

0.000211

Gnomad4 AMR exome

AF:

0.000875

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000355

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000924

Gnomad4 OTH exome

AF:

0.000987

GnomAD4 genome

AF:

0.000558

AC:

AN:

152310

Hom.:

Cov.:

AF XY:

0.000591

AC XY:

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.000980

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000926

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000634

Hom.:

Bravo

AF:

0.000699

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ExAC

AF:

0.000637

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.025

Eigen

Uncertain

0.22

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.87

M_CAP

Uncertain

0.088

MetaRNN

Benign

0.054

MetaSVM

Benign

-0.85

MutationAssessor

Uncertain

2.0

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.96

REVEL

Benign

0.23

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.95

Vest4

0.54

MVP

0.33

MPC

0.086

ClinPred

0.094

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.50

gMVP

0.13

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over