7-78194930-C-T

Position:

chr7-78194930-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_012301.4(MAGI2):c.2213G>A(p.Arg738Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00222 in 1,613,880 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 11 hom. )

Consequence

MAGI2
NM_012301.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 2.16

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:

LOC124901684 (HGNC:):

LOC124901684 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00938037).

BP6

Variant 7-78194930-C-T is Benign according to our data. Variant chr7-78194930-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 129559.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-78194930-C-T is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAdExome4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGI2	NM_012301.4 linkuse as main transcript	c.2213G>A	p.Arg738Gln	missense_variant	12/22	ENST00000354212.9	NP_036433.2
LOC124901684	XR_007060400.1 linkuse as main transcript	n.421+9324C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGI2	ENST00000354212.9 linkuse as main transcript	c.2213G>A	p.Arg738Gln	missense_variant	12/22	1	NM_012301.4	ENSP00000346151	P4	Q86UL8-1

Frequencies

GnomAD3 genomes

AF:

0.00158

AC:

241

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000748

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00311

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00237

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00198

AC:

496

AN:

250932

Hom.:

AF XY:

0.00223

AC XY:

303

AN XY:

135630

show subpopulations

Gnomad AFR exome

AF:

0.000554

Gnomad AMR exome

AF:

0.000986

Gnomad ASJ exome

AF:

0.00248

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.00347

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00270

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.00229

AC:

3344

AN:

1461606

Hom.:

Cov.:

AF XY:

0.00239

AC XY:

1738

AN XY:

727124

show subpopulations

Gnomad4 AFR exome

AF:

0.000478

Gnomad4 AMR exome

AF:

0.00101

Gnomad4 ASJ exome

AF:

0.00191

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00409

Gnomad4 FIN exome

AF:

0.000150

Gnomad4 NFE exome

AF:

0.00240

Gnomad4 OTH exome

AF:

0.00240

GnomAD4 genome

AF:

0.00158

AC:

241

AN:

152274

Hom.:

Cov.:

AF XY:

0.00154

AC XY:

115

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.000746

Gnomad4 AMR

AF:

0.00150

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00311

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00237

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.00224

Hom.:

Bravo

AF:

0.00174

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00186

AC:

ExAC

AF:

0.00204

AC:

248

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00317

EpiControl

AF:

0.00291

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2023	MAGI2: BS2 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Aug 01, 2013	- -
Likely benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Aug 21, 2015	- -

MAGI2-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 29, 2021

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.46

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.065

T;T;.;.;.;.;T;.;.;.;T;.

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.94

D;D;D;D;D;D;D;D;D;D;D;D

M_CAP

Benign

0.0054

MetaRNN

Benign

0.0094

T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.7

.;L;L;.;.;.;.;.;.;.;.;.

MutationTaster

Benign

0.93

D;D;D

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-0.93

.;N;N;.;.;.;.;N;.;.;.;.

REVEL

Benign

0.077

Sift

Benign

0.043

.;D;T;.;.;.;.;T;.;.;.;.

Sift4G

Benign

0.24

T;T;T;T;T;.;T;T;.;T;.;.

Polyphen

0.96, 0.98, 0.91

.;D;D;.;.;.;.;P;.;.;.;.

Vest4

0.46, 0.41, 0.47, 0.56, 0.53, 0.50

MVP

0.14

MPC

0.36

ClinPred

0.017

GERP RS

5.8

Varity_R

0.13

gMVP

0.33

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