dbSNP rs2074641: MAGI2:p.Leu1119Leu (chr7-78127263-T-C) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_012301.4(MAGI2):c.3357A>G(p.Leu1119Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.857 in 1,610,004 control chromosomes in the GnomAD database, including 594,423 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.86 ( 56239 hom., cov: 31)

Exomes 𝑓: 0.86 ( 538184 hom. )

Consequence

MAGI2
NM_012301.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.466

Variant links:

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]

MAGI2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 7-78127263-T-C is Benign according to our data. Variant chr7-78127263-T-C is described in ClinVar as [Benign]. Clinvar id is 129565.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-78127263-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.466 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.9 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGI2	NM_012301.4 link	c.3357A>G	p.Leu1119Leu	synonymous_variant	Exon 19 of 22	ENST00000354212.9	NP_036433.2	Q86UL8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGI2	ENST00000354212.9 link	c.3357A>G	p.Leu1119Leu	synonymous_variant	Exon 19 of 22	1	NM_012301.4	ENSP00000346151.4		Q86UL8-1

Frequencies

GnomAD3 genomes

AF:

0.857

AC:

130250

AN:

152032

Hom.:

56191

Cov.:

show subpopulations

Gnomad AFR

AF:

0.908

Gnomad AMI

AF:

0.694

Gnomad AMR

AF:

0.768

Gnomad ASJ

AF:

0.795

Gnomad EAS

AF:

0.589

Gnomad SAS

AF:

0.764

Gnomad FIN

AF:

0.870

Gnomad MID

AF:

0.801

Gnomad NFE

AF:

0.876

Gnomad OTH

AF:

0.845

GnomAD3 exomes

AF:

0.815

AC:

201791

AN:

247526

Hom.:

83566

AF XY:

0.817

AC XY:

109418

AN XY:

133898

show subpopulations

Gnomad AFR exome

AF:

0.912

Gnomad AMR exome

AF:

0.696

Gnomad ASJ exome

AF:

0.791

Gnomad EAS exome

AF:

0.579

Gnomad SAS exome

AF:

0.776

Gnomad FIN exome

AF:

0.872

Gnomad NFE exome

AF:

0.877

Gnomad OTH exome

AF:

0.829

GnomAD4 exome

AF:

0.857

AC:

1249121

AN:

1457854

Hom.:

538184

Cov.:

AF XY:

0.854

AC XY:

619599

AN XY:

725136

show subpopulations

Gnomad4 AFR exome

AF:

0.913

Gnomad4 AMR exome

AF:

0.707

Gnomad4 ASJ exome

AF:

0.802

Gnomad4 EAS exome

AF:

0.594

Gnomad4 SAS exome

AF:

0.769

Gnomad4 FIN exome

AF:

0.876

Gnomad4 NFE exome

AF:

0.878

Gnomad4 OTH exome

AF:

0.844

GnomAD4 genome

AF:

0.857

AC:

130356

AN:

152150

Hom.:

56239

Cov.:

AF XY:

0.849

AC XY:

63100

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.908

Gnomad4 AMR

AF:

0.768

Gnomad4 ASJ

AF:

0.795

Gnomad4 EAS

AF:

0.589

Gnomad4 SAS

AF:

0.764

Gnomad4 FIN

AF:

0.870

Gnomad4 NFE

AF:

0.876

Gnomad4 OTH

AF:

0.847

Alfa

AF:

0.862

Hom.:

103105

Bravo

AF:

0.850

Asia WGS

AF:

0.730

AC:

2542

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Apr 20, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 20, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:2

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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. -

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 92% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 86. Only high quality variants are reported. -

Nephrotic syndrome 15

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

6.9

DANN

Benign

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over