X-54809927-CA-TG

Variant names:

• chrX-54809927-CA-TG
• NM_177433.3:c.251_252delCAinsTG

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_177433.3(MAGED2):​c.251_252delCAinsTG​(p.Ser84Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. The variant is present in control chromosomes in GnomAd MNV project. The variant allele was found at a frequency of 0.0000126 in 2 alleles, including 0 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Synonymous variant affecting the same amino acid position (i.e. S84S) has been classified as Uncertain significance.

• Frequency: GnomAD MNV: 𝑓 0.000013 Genomes: not found (cov: 21)
• Consequence: MAGED2 NM_177433.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.10
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGED2	NM_177433.3	MANE Select	c.251_252delCAinsTG	p.Ser84Leu	missense	N/A	NP_803182.1	Q9UNF1-1
	MAGED2	NM_014599.6		c.251_252delCAinsTG	p.Ser84Leu	missense	N/A	NP_055414.2
	MAGED2	NM_201222.3		c.251_252delCAinsTG	p.Ser84Leu	missense	N/A	NP_957516.1	Q9UNF1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGED2	ENST00000375068.6	TSL:1 MANE Select	c.251_252delCAinsTG	p.Ser84Leu	missense	N/A	ENSP00000364209.1	Q9UNF1-1
	MAGED2	ENST00000375053.6	TSL:1	c.251_252delCAinsTG	p.Ser84Leu	missense	N/A	ENSP00000364193.2	Q9UNF1-1
	MAGED2	ENST00000375058.5	TSL:1	c.251_252delCAinsTG	p.Ser84Leu	missense	N/A	ENSP00000364198.1	Q9UNF1-1

Frequencies

GnomAD3 genomes Cov.: 21

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 21

GnomAD MNV AF: 0.0000126 AC: 2 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1

Splicing

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

Other links and lift over

hg19: chrX-54836360;