chrX-54810017-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_177433.3(MAGED2):c.341A>G(p.Gln114Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000151 in 1,205,111 control chromosomes in the GnomAD database, including 1 homozygotes. There are 70 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.000063 ( 0 hom., 3 hem., cov: 21)

Exomes 𝑓: 0.00016 ( 1 hom. 67 hem. )

Consequence

MAGED2
NM_177433.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.05

Publications

1 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: DEFINITIVE, STRONG Submitted by: ClinGen, 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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009059906).

BP6

Variant X-54810017-A-G is Benign according to our data. Variant chrX-54810017-A-G is described in ClinVar as Benign. ClinVar VariationId is 2762939.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 3 XL,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_177433.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAGED2	NM_177433.3	MANE Select	c.341A>G	p.Gln114Arg	missense	Exon 3 of 13	NP_803182.1	Q9UNF1-1
MAGED2	NM_014599.6		c.341A>G	p.Gln114Arg	missense	Exon 3 of 13	NP_055414.2
MAGED2	NM_201222.3		c.341A>G	p.Gln114Arg	missense	Exon 3 of 13	NP_957516.1	Q9UNF1-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAGED2	ENST00000375068.6	TSL:1 MANE Select	c.341A>G	p.Gln114Arg	missense	Exon 3 of 13	ENSP00000364209.1	Q9UNF1-1
MAGED2	ENST00000375053.6	TSL:1	c.341A>G	p.Gln114Arg	missense	Exon 3 of 12	ENSP00000364193.2	Q9UNF1-1
MAGED2	ENST00000375058.5	TSL:1	c.341A>G	p.Gln114Arg	missense	Exon 3 of 13	ENSP00000364198.1	Q9UNF1-1

Frequencies

GnomAD3 genomes

AF:

0.0000632

AC:

AN:

110753

Hom.:

Cov.:

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:

0.00198

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

GnomAD2 exomes

AF:

0.000110

AC:

AN:

172511

AF XY:

0.000120

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00143

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000160

AC:

175

AN:

1094306

Hom.:

Cov.:

AF XY:

0.000186

AC XY:

AN XY:

360240

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26364

American (AMR)

AF:

0.00

AC:

AN:

34828

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19270

East Asian (EAS)

AF:

0.00580

AC:

175

AN:

30161

South Asian (SAS)

AF:

0.00

AC:

AN:

53431

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40148

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4130

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

839997

Other (OTH)

AF:

0.00

AC:

AN:

45977

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.0000632

AC:

AN:

110805

Hom.:

Cov.:

AF XY:

0.0000909

AC XY:

AN XY:

32993

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30446

American (AMR)

AF:

0.00

AC:

AN:

10529

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2630

East Asian (EAS)

AF:

0.00199

AC:

AN:

3521

South Asian (SAS)

AF:

0.00

AC:

AN:

2472

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6017

Middle Eastern (MID)

AF:

0.00

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

52782

Other (OTH)

AF:

0.00

AC:

AN:

1514

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.00

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.000157

AC:

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.87

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.020

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.60

M_CAP

Benign

0.014

MetaRNN

Benign

0.0091

MetaSVM

Benign

-0.83

MutationAssessor

Benign

1.1

PhyloP100

1.0

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.98

REVEL

Benign

0.031

Sift

Benign

0.097

Sift4G

Benign

0.53

Polyphen

0.29

Vest4

0.037

MVP

0.56

MPC

0.65

ClinPred

0.084

GERP RS

3.2

Varity_R

0.12

gMVP

0.12

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over