rs76346657
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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):āc.2329T>Cā(p.Leu777=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00123 in 1,612,356 control chromosomes in the GnomAD database, including 20 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 0.0068 ( 11 hom., cov: 32)
Exomes š: 0.00066 ( 9 hom. )
Consequence
MAGI2
NM_012301.4 synonymous
NM_012301.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.00800
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=-0.55).
BP6
?
Variant 7-78178085-A-G is Benign according to our data. Variant chr7-78178085-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 129560.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.008 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00676 (1029/152286) while in subpopulation AFR AF= 0.0233 (968/41558). AF 95% confidence interval is 0.0221. There are 11 homozygotes in gnomad4. There are 492 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 11 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MAGI2 | NM_012301.4 | c.2329T>C | p.Leu777= | synonymous_variant | 14/22 | ENST00000354212.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAGI2 | ENST00000354212.9 | c.2329T>C | p.Leu777= | synonymous_variant | 14/22 | 1 | NM_012301.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00678 AC: 1032AN: 152168Hom.: 11 Cov.: 32
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GnomAD3 exomes AF: 0.00177 AC: 444AN: 250942Hom.: 0 AF XY: 0.00131 AC XY: 178AN XY: 135600
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GnomAD4 exome AF: 0.000655 AC: 957AN: 1460070Hom.: 9 Cov.: 29 AF XY: 0.000529 AC XY: 384AN XY: 726416
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GnomAD4 genome ? AF: 0.00676 AC: 1029AN: 152286Hom.: 11 Cov.: 32 AF XY: 0.00661 AC XY: 492AN XY: 74452
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
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 | Jan 25, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 02, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
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