Variant NM_002364.5:c.647A>C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002364.5(MAGEB2):c.647A>C(p.Asn216Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000897 in 111,502 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 0 hem., cov: 23)

Consequence

MAGEB2
NM_002364.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.28

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGEB2	NM_002364.5 link	c.647A>C	p.Asn216Thr	missense_variant	Exon 2 of 2	ENST00000378988.5	NP_002355.2	O15479Q53G50
MAGEB2	XM_011545512.2 link	c.647A>C	p.Asn216Thr	missense_variant	Exon 2 of 2		XP_011543814.1	O15479

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGEB2	ENST00000378988.5 link	c.647A>C	p.Asn216Thr	missense_variant	Exon 2 of 2	1	NM_002364.5	ENSP00000368273.4		O15479

Frequencies

GnomAD3 genomes

AF:

0.00000897

AC:

AN:

111449

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33655

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000281

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000549

AC:

AN:

182177

Hom.:

AF XY:

0.00

AC XY:

AN XY:

66675

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000725

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000897

AC:

AN:

111502

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33718

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000282

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.18

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.66

M_CAP

Benign

0.0033

MetaRNN

Uncertain

0.55

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.7

PrimateAI

Benign

0.45

PROVEAN

Pathogenic

-5.7

REVEL

Benign

0.084

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0030

Polyphen

0.99

Vest4

0.27

MutPred

0.81

Loss of helix (P = 0.2022);

MVP

0.26

MPC

0.0083

ClinPred

0.95

GERP RS

3.3

Varity_R

0.60

gMVP

0.38

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