Variant 4-78887246-A-G 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.2024A>G(p.Glu675Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000622 in 1,611,414 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00083 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00060 ( 3 hom. )

Consequence

BMP2K
NM_198892.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.16

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=0.021440357).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMP2K	NM_198892.2 linkuse as main transcript	c.2024A>G	p.Glu675Gly	missense_variant	15/16	ENST00000502613.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMP2K	ENST00000502613.3 linkuse as main transcript	c.2024A>G	p.Glu675Gly	missense_variant	15/16	1	NM_198892.2	P1	Q9NSY1-1
PAQR3	ENST00000342820.10 linkuse as main transcript	c.*988T>C		3_prime_UTR_variant, NMD_transcript_variant	13/13	1
PAQR3	ENST00000512760.5 linkuse as main transcript	c.*910T>C		3_prime_UTR_variant, NMD_transcript_variant	9/9	1			Q6TCH7-4

Frequencies

GnomAD3 genomes

AF:

0.000835

AC:

127

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00334

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000809

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000920

AC:

226

AN:

245670

Hom.:

AF XY:

0.00104

AC XY:

139

AN XY:

133068

show subpopulations

Gnomad AFR exome

AF:

0.0000655

Gnomad AMR exome

AF:

0.000996

Gnomad ASJ exome

AF:

0.00201

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00128

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00115

Gnomad OTH exome

AF:

0.000833

GnomAD4 exome

AF:

0.000600

AC:

875

AN:

1459124

Hom.:

Cov.:

AF XY:

0.000699

AC XY:

507

AN XY:

725524

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000944

Gnomad4 ASJ exome

AF:

0.00230

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00125

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000497

Gnomad4 OTH exome

AF:

0.00121

GnomAD4 genome

AF:

0.000834

AC:

127

AN:

152290

Hom.:

Cov.:

AF XY:

0.000967

AC XY:

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.00333

Gnomad4 ASJ

AF:

0.00231

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000809

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000960

Hom.:

Bravo

AF:

0.000827

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00109

AC:

ExAC

AF:

0.000968

AC:

117

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 22, 2021

The c.2024A>G (p.E675G) alteration is located in exon 15 (coding exon 15) of the BMP2K gene. This alteration results from a A to G substitution at nucleotide position 2024, causing the glutamic acid (E) at amino acid position 675 to be replaced by a glycine (G). 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

0.16

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.093

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.63

M_CAP

Benign

0.025

MetaRNN

Benign

0.021

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.20

Sift

Uncertain

0.024

Sift4G

Benign

0.13

Polyphen

1.0

Vest4

0.36

MVP

0.30

MPC

0.093

ClinPred

0.070

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.20

gMVP

0.22

Splicing

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over