rs146012909

Variant names:

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_012301.4(MAGI2):c.276C>G(p.Pro92Pro) 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 (★★).

Frequency

Genomes: 𝑓 0.0060 ( 2 hom., cov: 32)

Exomes 𝑓: 0.010 ( 127 hom. )

Consequence

MAGI2
NM_012301.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 1.03

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:

MAGI2-AS3 (HGNC:40862): (MAGI2 antisense RNA 3)

MAGI2-AS3 links:

Genome browser will be placed here

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 rank	MANE	Protein	UniProt
MAGI2	NM_012301.4 link	c.276C>G	p.Pro92Pro	synonymous_variant	Exon 1 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.276C>G	p.Pro92Pro	synonymous_variant	Exon 1 of 22	1	NM_012301.4	ENSP00000346151.4		Q86UL8-1

Frequencies

GnomAD3 genomes

AF:

0.00597

AC:

909

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00166

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.00196

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00766

Gnomad FIN

AF:

0.00207

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0107

Gnomad OTH

AF:

0.00334

GnomAD3 exomes

AF:

0.00676

AC:

1635

AN:

242030

Hom.:

AF XY:

0.00725

AC XY:

948

AN XY:

130692

show subpopulations

Gnomad AFR exome

AF:

0.00217

Gnomad AMR exome

AF:

0.00142

Gnomad ASJ exome

AF:

0.00154

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0106

Gnomad FIN exome

AF:

0.00176

Gnomad NFE exome

AF:

0.0106

Gnomad OTH exome

AF:

0.00664

GnomAD4 exome

AF:

0.0105

AC:

15165

AN:

1450066

Hom.:

127

Cov.:

AF XY:

0.0103

AC XY:

7424

AN XY:

720146

show subpopulations

Gnomad4 AFR exome

AF:

0.00126

Gnomad4 AMR exome

AF:

0.00143

Gnomad4 ASJ exome

AF:

0.00147

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.0112

Gnomad4 FIN exome

AF:

0.00208

Gnomad4 NFE exome

AF:

0.0123

Gnomad4 OTH exome

AF:

0.00661

GnomAD4 genome

AF:

0.00596

AC:

908

AN:

152314

Hom.:

Cov.:

AF XY:

0.00549

AC XY:

409

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00166

Gnomad4 AMR

AF:

0.00196

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00746

Gnomad4 FIN

AF:

0.00207

Gnomad4 NFE

AF:

0.0107

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00708

Hom.:

Bravo

AF:

0.00567

Asia WGS

AF:

0.00289

AC:

AN:

3478

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

Jan 26, 2018

Athena Diagnostics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

MAGI2: BP4, BP7, BS1, BS2; MAGI2-AS3: BS1, BS2 -

Mar 19, 2020

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Nov 11, 2013

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

MAGI2-related disorder

Benign:1

Mar 05, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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). -

Nephrotic syndrome 15

Benign:1

Aug 22, 2021

Fulgent Genetics, Fulgent Genetics

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

-0.43

CADD

Benign

DANN

Benign

0.88

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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