Variant X-54809253-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_177433.3(MAGED2):c.-29-50G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0185 in 1,021,108 control chromosomes in the GnomAD database, including 155 homozygotes. There are 5,141 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 6 hom., 391 hem., cov: 23)

Exomes 𝑓: 0.019 ( 149 hom. 4750 hem. )

Consequence

MAGED2
NM_177433.3 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.150

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant X-54809253-G-T is Benign according to our data. Variant chrX-54809253-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1213451.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0121 (1349/111748) while in subpopulation NFE AF= 0.0198 (1051/53044). AF 95% confidence interval is 0.0188. There are 6 homozygotes in gnomad4. There are 391 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
MAGED2	NM_177433.3 linkuse as main transcript	c.-29-50G>T	intron_variant	ENST00000375068.6	NP_803182.1
MAGED2	NM_014599.6 linkuse as main transcript	c.-29-50G>T	intron_variant		NP_055414.2
MAGED2	NM_201222.3 linkuse as main transcript	c.-30+30G>T	intron_variant		NP_957516.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGED2	ENST00000375068.6 linkuse as main transcript	c.-29-50G>T		intron_variant		1	NM_177433.3	ENSP00000364209	P1	Q9UNF1-1

Frequencies

GnomAD3 genomes

AF:

0.0121

AC:

1350

AN:

111691

Hom.:

Cov.:

AF XY:

0.0115

AC XY:

391

AN XY:

33869

show subpopulations

Gnomad AFR

AF:

0.00277

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00348

Gnomad ASJ

AF:

0.00604

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00262

Gnomad FIN

AF:

0.0235

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0198

Gnomad OTH

AF:

0.00802

GnomAD4 exome

AF:

0.0193

AC:

17515

AN:

909360

Hom.:

149

Cov.:

AF XY:

0.0184

AC XY:

4750

AN XY:

258300

show subpopulations

Gnomad4 AFR exome

AF:

0.00184

Gnomad4 AMR exome

AF:

0.00250

Gnomad4 ASJ exome

AF:

0.00713

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00181

Gnomad4 FIN exome

AF:

0.0248

Gnomad4 NFE exome

AF:

0.0232

Gnomad4 OTH exome

AF:

0.0144

GnomAD4 genome

AF:

0.0121

AC:

1349

AN:

111748

Hom.:

Cov.:

AF XY:

0.0115

AC XY:

391

AN XY:

33936

show subpopulations

Gnomad4 AFR

AF:

0.00276

Gnomad4 AMR

AF:

0.00348

Gnomad4 ASJ

AF:

0.00604

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00225

Gnomad4 FIN

AF:

0.0235

Gnomad4 NFE

AF:

0.0198

Gnomad4 OTH

AF:

0.00791

Alfa

AF:

0.0176

Hom.:

101

Bravo

AF:

0.0103

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 01, 2020	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

3.7

DANN

Benign

0.68

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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