Variant X-54809928-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_177433.3(MAGED2):c.252A>G(p.Ser84=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 1,196,048 control chromosomes in the GnomAD database, including 51,377 homozygotes. There are 137,072 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 4686 hom., 10959 hem., cov: 21)

Exomes 𝑓: 0.35 ( 46691 hom. 126113 hem. )

Consequence

MAGED2
NM_177433.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.10

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 -21 ACMG points.

BP4

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

BP6

Variant X-54809928-A-G is Benign according to our data. Variant chrX-54809928-A-G is described in ClinVar as [Benign]. Clinvar id is 1244776.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-54809928-A-G is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=1.1 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.595 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MAGED2	NM_177433.3 linkuse as main transcript	c.252A>G	p.Ser84=	synonymous_variant	3/13	ENST00000375068.6	NP_803182.1
MAGED2	NM_014599.6 linkuse as main transcript	c.252A>G	p.Ser84=	synonymous_variant	3/13		NP_055414.2
MAGED2	NM_201222.3 linkuse as main transcript	c.252A>G	p.Ser84=	synonymous_variant	3/13		NP_957516.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGED2	ENST00000375068.6 linkuse as main transcript	c.252A>G	p.Ser84=	synonymous_variant	3/13	1	NM_177433.3	ENSP00000364209	P1	Q9UNF1-1

Frequencies

GnomAD3 genomes

AF:

0.341

AC:

37391

AN:

109663

Hom.:

4698

Cov.:

AF XY:

0.342

AC XY:

10935

AN XY:

31957

show subpopulations

Gnomad AFR

AF:

0.303

Gnomad AMI

AF:

0.108

Gnomad AMR

AF:

0.365

Gnomad ASJ

AF:

0.372

Gnomad EAS

AF:

0.617

Gnomad SAS

AF:

0.369

Gnomad FIN

AF:

0.397

Gnomad MID

AF:

0.244

Gnomad NFE

AF:

0.334

Gnomad OTH

AF:

0.332

GnomAD3 exomes

AF:

0.367

AC:

57632

AN:

157094

Hom.:

7775

AF XY:

0.361

AC XY:

17544

AN XY:

48626

show subpopulations

Gnomad AFR exome

AF:

0.294

Gnomad AMR exome

AF:

0.329

Gnomad ASJ exome

AF:

0.376

Gnomad EAS exome

AF:

0.622

Gnomad SAS exome

AF:

0.386

Gnomad FIN exome

AF:

0.398

Gnomad NFE exome

AF:

0.337

Gnomad OTH exome

AF:

0.326

GnomAD4 exome

AF:

0.353

AC:

383735

AN:

1086329

Hom.:

46691

Cov.:

AF XY:

0.355

AC XY:

126113

AN XY:

355205

show subpopulations

Gnomad4 AFR exome

AF:

0.303

Gnomad4 AMR exome

AF:

0.336

Gnomad4 ASJ exome

AF:

0.378

Gnomad4 EAS exome

AF:

0.636

Gnomad4 SAS exome

AF:

0.388

Gnomad4 FIN exome

AF:

0.403

Gnomad4 NFE exome

AF:

0.341

Gnomad4 OTH exome

AF:

0.349

GnomAD4 genome

AF:

0.341

AC:

37388

AN:

109719

Hom.:

4686

Cov.:

AF XY:

0.342

AC XY:

10959

AN XY:

32023

show subpopulations

Gnomad4 AFR

AF:

0.303

Gnomad4 AMR

AF:

0.364

Gnomad4 ASJ

AF:

0.372

Gnomad4 EAS

AF:

0.617

Gnomad4 SAS

AF:

0.367

Gnomad4 FIN

AF:

0.397

Gnomad4 NFE

AF:

0.334

Gnomad4 OTH

AF:

0.328

Alfa

AF:

0.338

Hom.:

15443

Bravo

AF:

0.341

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 08, 2018	- -

Bartter disease type 5

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

9.9

DANN

Benign

0.80

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