chrX-54809806-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_177433.3(MAGED2):c.130A>G(p.Lys44Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00455 in 1,200,730 control chromosomes in the GnomAD database, including 11 homozygotes. There are 1,745 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0027 ( 1 hom., 74 hem., cov: 22)

Exomes 𝑓: 0.0047 ( 10 hom. 1671 hem. )

Consequence

MAGED2
NM_177433.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.21

Publications

4 publications found

Variant links:

Genes affected

MAGED2 (HGNC:16353): (MAGE family member D2) This gene is a member of the MAGED gene family. The MAGED genes are clustered on chromosome Xp11. This gene is located in Xp11.2, a hot spot for X-linked intellectual disability (XLID). Mutations in this gene cause a form of transient antenatal Bartter's syndrome. This gene may also be involved in several types of cancer, including breast cancer and melanoma. The protein encoded by this gene is progressively recruited from the cytoplasm to the nucleoplasm during the interphase and after nucleolar stress and is thus thought to play a role in cell cycle regulation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2017]

MAGED2 Gene-Disease associations (from GenCC):

Bartter disease type 5
Inheritance: XL Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
antenatal Bartter syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

MAGED2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0052116513).

BP6

Variant X-54809806-A-G is Benign according to our data. Variant chrX-54809806-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 445992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Hemizygotes in GnomAd4 at 74 XL,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGED2	NM_177433.3 link	c.130A>G	p.Lys44Glu	missense_variant	Exon 3 of 13	ENST00000375068.6	NP_803182.1	Q9UNF1-1A0A024R9Y7
MAGED2	NM_014599.6 link	c.130A>G	p.Lys44Glu	missense_variant	Exon 3 of 13		NP_055414.2	Q9UNF1-1A0A024R9Y7
MAGED2	NM_201222.3 link	c.130A>G	p.Lys44Glu	missense_variant	Exon 3 of 13		NP_957516.1	Q9UNF1-1A0A024R9Y7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGED2	ENST00000375068.6 link	c.130A>G	p.Lys44Glu	missense_variant	Exon 3 of 13	1	NM_177433.3	ENSP00000364209.1		Q9UNF1-1

Frequencies

GnomAD3 genomes

AF:

0.00272

AC:

301

AN:

110849

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000791

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000857

Gnomad ASJ

AF:

0.00151

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000787

Gnomad FIN

AF:

0.00101

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00478

Gnomad OTH

AF:

0.00200

GnomAD2 exomes

AF:

0.00317

AC:

520

AN:

163982

AF XY:

0.00340

show subpopulations

Gnomad AFR exome

AF:

0.000682

Gnomad AMR exome

AF:

0.000777

Gnomad ASJ exome

AF:

0.00209

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000820

Gnomad NFE exome

AF:

0.00591

Gnomad OTH exome

AF:

0.00312

GnomAD4 exome

AF:

0.00474

AC:

5166

AN:

1089826

Hom.:

Cov.:

AF XY:

0.00469

AC XY:

1671

AN XY:

356358

show subpopulations

African (AFR)

AF:

0.000647

AC:

AN:

26257

American (AMR)

AF:

0.000731

AC:

AN:

34220

Ashkenazi Jewish (ASJ)

AF:

0.00208

AC:

AN:

19232

East Asian (EAS)

AF:

0.00

AC:

AN:

29921

South Asian (SAS)

AF:

0.00180

AC:

AN:

52709

European-Finnish (FIN)

AF:

0.00110

AC:

AN:

39999

Middle Eastern (MID)

AF:

0.000243

AC:

AN:

4112

European-Non Finnish (NFE)

AF:

0.00571

AC:

4783

AN:

837580

Other (OTH)

AF:

0.00352

AC:

161

AN:

45796

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

187

374

562

749

936

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

188

376

564

752

940

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00271

AC:

301

AN:

110904

Hom.:

Cov.:

AF XY:

0.00223

AC XY:

AN XY:

33126

show subpopulations

African (AFR)

AF:

0.000789

AC:

AN:

30413

American (AMR)

AF:

0.000856

AC:

AN:

10511

Ashkenazi Jewish (ASJ)

AF:

0.00151

AC:

AN:

2641

East Asian (EAS)

AF:

0.00

AC:

AN:

3514

South Asian (SAS)

AF:

0.000788

AC:

AN:

2537

European-Finnish (FIN)

AF:

0.00101

AC:

AN:

5967

Middle Eastern (MID)

AF:

0.00

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.00478

AC:

253

AN:

52901

Other (OTH)

AF:

0.00197

AC:

AN:

1522

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00401

Hom.:

183

Bravo

AF:

0.00263

TwinsUK

AF:

0.00512

AC:

ALSPAC

AF:

0.00554

AC:

ESP6500AA

AF:

0.00156

AC:

ESP6500EA

AF:

0.00505

AC:

ExAC

AF:

0.00306

AC:

370

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Dec 15, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 16, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.019

T;T;T;T;T;T;T;T

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.70

.;T;.;T;T;.;.;.

M_CAP

Benign

0.0077

MetaRNN

Benign

0.0052

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.1

L;.;L;.;L;L;.;L

PhyloP100

1.2

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.43

N;.;N;N;N;N;N;N

REVEL

Benign

0.22

Sift

Uncertain

0.0020

D;.;D;D;D;D;T;D

Sift4G

Benign

1.0

T;T;T;T;T;T;T;T

Polyphen

0.98

D;P;D;.;D;D;P;D

Vest4

0.068

MVP

0.66

MPC

0.88

ClinPred

0.027

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.26

gMVP

0.44

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over