Variant X-30219169-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000378988.5(MAGEB2):c.589G>C(p.Asp197His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000108 in 1,208,653 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000090 ( 0 hom., 4 hem., cov: 23)

Exomes 𝑓: 0.0000027 ( 0 hom. 1 hem. )

Consequence

MAGEB2
ENST00000378988.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.146

Variant links:

Genes affected

MAGEB2 (HGNC:6809): (MAGE family member B2) This gene is a member of the MAGEB gene family. The members of this family have their entire coding sequences located in the last exon, and the encoded proteins show 50 to 68% sequence identity to each other. The promoters and first exons of the MAGEB genes show considerable variability, suggesting that the existence of this gene family enables the same function to be expressed under different transcriptional controls. This gene is localized in the DSS (dosage-sensitive sex reversal) critical region. It is expressed in testis and placenta, and in a significant fraction of tumors of various histological types. The MAGEB genes are clustered on chromosome Xp22-p21. [provided by RefSeq, Jul 2008]

MAGEB2 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=0.049815893).

BS2

High Hemizygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGEB2	NM_002364.5 linkuse as main transcript	c.589G>C	p.Asp197His	missense_variant	2/2	ENST00000378988.5	NP_002355.2
MAGEB2	XM_011545512.2 linkuse as main transcript	c.589G>C	p.Asp197His	missense_variant	2/2		XP_011543814.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGEB2	ENST00000378988.5 linkuse as main transcript	c.589G>C	p.Asp197His	missense_variant	2/2	1	NM_002364.5	ENSP00000368273	P1

Frequencies

GnomAD3 genomes

AF:

0.0000899

AC:

AN:

111282

Hom.:

Cov.:

AF XY:

0.000119

AC XY:

AN XY:

33482

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000761

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:

0.00

Gnomad OTH

AF:

0.00135

GnomAD4 exome

AF:

0.00000273

AC:

AN:

1097318

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

362698

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000284

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:

0.00000238

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000898

AC:

AN:

111335

Hom.:

Cov.:

AF XY:

0.000119

AC XY:

AN XY:

33545

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000760

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00133

Bravo

AF:

0.000102

ExAC

AF:

0.0000165

AC:

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

Jan 03, 2024

The c.589G>C (p.D197H) alteration is located in exon 2 (coding exon 1) of the MAGEB2 gene. This alteration results from a G to C substitution at nucleotide position 589, causing the aspartic acid (D) at amino acid position 197 to be replaced by a histidine (H). 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

0.15

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.94

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.014

FATHMM_MKL

Benign

0.054

LIST_S2

Benign

0.20

M_CAP

Benign

0.0024

MetaRNN

Benign

0.050

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

MutationTaster

Benign

1.0

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.8

REVEL

Benign

0.030

Sift

Benign

0.040

Sift4G

Uncertain

0.031

Polyphen

0.84

Vest4

0.071

MutPred

0.40

Loss of ubiquitination at K202 (P = 0.1103);

MVP

0.20

MPC

0.0056

ClinPred

0.32

GERP RS

-0.63

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.069

gMVP

0.47

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over