rs146012909
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_012301.4(MAGI2):āc.276C>Gā(p.Pro92=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.01 in 1,602,380 control chromosomes in the GnomAD database, including 129 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.0060 ( 2 hom., cov: 32)
Exomes š: 0.010 ( 127 hom. )
Consequence
MAGI2
NM_012301.4 synonymous
NM_012301.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.03
Genes affected
MAGI2 (HGNC:18957): (membrane associated guanylate kinase, WW and PDZ domain containing 2) The protein encoded by this gene interacts with atrophin-1. Atrophin-1 contains a polyglutamine repeat, expansion of which is responsible for dentatorubral and pallidoluysian atrophy. This encoded protein is characterized by two WW domains, a guanylate kinase-like domain, and multiple PDZ domains. It has structural similarity to the membrane-associated guanylate kinase homologue (MAGUK) family. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
?
Variant 7-79453045-G-C is Benign according to our data. Variant chr7-79453045-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 95511.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-79453045-G-C is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=1.03 with no splicing effect.
BS2
?
High Homozygotes in GnomAd4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MAGI2 | NM_012301.4 | c.276C>G | p.Pro92= | synonymous_variant | 1/22 | ENST00000354212.9 | |
MAGI2-AS3 | NR_038346.1 | n.89G>C | non_coding_transcript_exon_variant | 1/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAGI2 | ENST00000354212.9 | c.276C>G | p.Pro92= | synonymous_variant | 1/22 | 1 | NM_012301.4 | P4 | |
MAGI2-AS3 | ENST00000426835.6 | n.43G>C | non_coding_transcript_exon_variant | 1/4 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00597 AC: 909AN: 152196Hom.: 2 Cov.: 32
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GnomAD3 exomes AF: 0.00676 AC: 1635AN: 242030Hom.: 14 AF XY: 0.00725 AC XY: 948AN XY: 130692
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GnomAD4 exome AF: 0.0105 AC: 15165AN: 1450066Hom.: 127 Cov.: 31 AF XY: 0.0103 AC XY: 7424AN XY: 720146
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GnomAD4 genome ? AF: 0.00596 AC: 908AN: 152314Hom.: 2 Cov.: 32 AF XY: 0.00549 AC XY: 409AN XY: 74460
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:4
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Oct 01, 2023 | MAGI2: BP4, BP7, BS1, BS2; MAGI2-AS3: BS1, BS2 - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 19, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jan 26, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 20, 2023 | - - |
MAGI2-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 05, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Nov 11, 2013 | - - |
Nephrotic syndrome 15 Benign:1
Benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Aug 22, 2021 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at