rs117054456
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_012301.4(MAGI2):c.3915G>A(p.Gln1305=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.035 in 1,612,638 control chromosomes in the GnomAD database, including 1,238 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.025 ( 79 hom., cov: 30)
Exomes 𝑓: 0.036 ( 1159 hom. )
Consequence
MAGI2
NM_012301.4 synonymous
NM_012301.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.30
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 -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.29).
BP6
?
Variant 7-78019768-C-T is Benign according to our data. Variant chr7-78019768-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 95512.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-78019768-C-T is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=2.3 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0251 (3807/151934) while in subpopulation NFE AF= 0.0409 (2779/67902). AF 95% confidence interval is 0.0397. There are 79 homozygotes in gnomad4. There are 1748 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 79 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MAGI2 | NM_012301.4 | c.3915G>A | p.Gln1305= | synonymous_variant | 22/22 | ENST00000354212.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAGI2 | ENST00000354212.9 | c.3915G>A | p.Gln1305= | synonymous_variant | 22/22 | 1 | NM_012301.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0251 AC: 3809AN: 151822Hom.: 79 Cov.: 30
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GnomAD3 exomes AF: 0.0252 AC: 6243AN: 247638Hom.: 124 AF XY: 0.0256 AC XY: 3435AN XY: 134092
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GnomAD4 exome AF: 0.0360 AC: 52650AN: 1460704Hom.: 1159 Cov.: 32 AF XY: 0.0355 AC XY: 25801AN XY: 726516
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GnomAD4 genome ? AF: 0.0251 AC: 3807AN: 151934Hom.: 79 Cov.: 30 AF XY: 0.0235 AC XY: 1748AN XY: 74290
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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 specified Benign:3
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 30, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jun 29, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Sep 05, 2012 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 14, 2021 | - - |
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