rs73703715
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_012301.4(MAGI2):c.2379C>T(p.Leu793=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00164 in 1,612,850 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0090 ( 29 hom., cov: 32)
Exomes 𝑓: 0.00088 ( 14 hom. )
Consequence
MAGI2
NM_012301.4 synonymous
NM_012301.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.128
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 -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.62).
BP6
Variant 7-78178035-G-A is Benign according to our data. Variant chr7-78178035-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 129561.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.128 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00899 (1368/152190) while in subpopulation AFR AF= 0.0317 (1314/41508). AF 95% confidence interval is 0.0302. There are 29 homozygotes in gnomad4. There are 696 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 29 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MAGI2 | NM_012301.4 | c.2379C>T | p.Leu793= | synonymous_variant | 14/22 | ENST00000354212.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAGI2 | ENST00000354212.9 | c.2379C>T | p.Leu793= | synonymous_variant | 14/22 | 1 | NM_012301.4 | P4 |
Frequencies
GnomAD3 genomes AF: 0.00890 AC: 1354AN: 152072Hom.: 29 Cov.: 32
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GnomAD3 exomes AF: 0.00243 AC: 610AN: 251126Hom.: 5 AF XY: 0.00183 AC XY: 249AN XY: 135710
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GnomAD4 exome AF: 0.000880 AC: 1285AN: 1460660Hom.: 14 Cov.: 29 AF XY: 0.000749 AC XY: 544AN XY: 726684
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GnomAD4 genome AF: 0.00899 AC: 1368AN: 152190Hom.: 29 Cov.: 32 AF XY: 0.00935 AC XY: 696AN XY: 74416
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Nov 20, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 19, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 18, 2021 | - - |
MAGI2-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 18, 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
Likely benign, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | - | Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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