NM_177433.3:c.991-2A>G
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PVS1_ModeratePM2PP5
The NM_177433.3(MAGED2):c.991-2A>G variant causes a splice acceptor, intron change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 23)
Exomes 𝑓: 9.7e-7 ( 0 hom. 1 hem. )
Failed GnomAD Quality Control
Consequence
MAGED2
NM_177433.3 splice_acceptor, intron
NM_177433.3 splice_acceptor, intron
Scores
1
1
3
Splicing: ADA: 1.000
2
Clinical Significance
Conservation
PhyloP100: 6.44
Publications
1 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 5Inheritance: XL Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
- antenatal Bartter syndromeInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 5 ACMG points.
PVS1
Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.052169137 fraction of the gene. Cryptic splice site detected, with MaxEntScore 3.5, offset of 21, new splice context is: tatttgggattcaattgaAGgaa. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant X-54812155-A-G is Pathogenic according to our data. Variant chrX-54812155-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 226032.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MAGED2 | NM_177433.3 | c.991-2A>G | splice_acceptor_variant, intron_variant | Intron 6 of 12 | ENST00000375068.6 | NP_803182.1 | ||
MAGED2 | NM_014599.6 | c.991-2A>G | splice_acceptor_variant, intron_variant | Intron 6 of 12 | NP_055414.2 | |||
MAGED2 | NM_201222.3 | c.991-2A>G | splice_acceptor_variant, intron_variant | Intron 6 of 12 | NP_957516.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 23
GnomAD3 genomes
Cov.:
23
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 9.73e-7 AC: 1AN: 1027391Hom.: 0 Cov.: 19 AF XY: 0.00000319 AC XY: 1AN XY: 313681 show subpopulations
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
1
AN:
1027391
Hom.:
Cov.:
19
AF XY:
AC XY:
1
AN XY:
313681
show subpopulations
African (AFR)
AF:
AC:
0
AN:
24983
American (AMR)
AF:
AC:
0
AN:
34873
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
18827
East Asian (EAS)
AF:
AC:
0
AN:
29683
South Asian (SAS)
AF:
AC:
0
AN:
52228
European-Finnish (FIN)
AF:
AC:
0
AN:
40221
Middle Eastern (MID)
AF:
AC:
0
AN:
3962
European-Non Finnish (NFE)
AF:
AC:
1
AN:
778924
Other (OTH)
AF:
AC:
0
AN:
43690
Age Distribution
Exome Hom
Variant carriers
0
2
4
6
8
10
<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 Cov.: 23
GnomAD4 genome
Cov.:
23
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Bartter disease type 5 Pathogenic:1
Sep 23, 2016
OMIM
Significance:Pathogenic
Review Status:no assertion criteria provided
Collection Method:literature only
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Benign
DANN
Benign
FATHMM_MKL
Uncertain
D
PhyloP100
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AL_spliceai
Position offset: 2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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