X-54809253-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.150

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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 GnomAd at 6 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAGED2	NM_177433.3	c.-29-50G>T		intron_variant		ENST00000375068.6
MAGED2	NM_014599.6	c.-29-50G>T		intron_variant
MAGED2	NM_201222.3	c.-30+30G>T		intron_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0121 AC: 1350 AN: 111691 Hom.: 6 Cov.: 23 AF XY: 0.0115 AC XY: 391 AN XY: 33869

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.: 15 AF XY: 0.0184 AC XY: 4750 AN XY: 258300

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.: 6 Cov.: 23 AF XY: 0.0115 AC XY: 391 AN XY: 33936

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 01, 2020

- -

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

Other links and lift over

dbSNP: rs41309825; hg19: chrX-54835686;