Variant chr7-78019493-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_012301.4(MAGI2):c.4190G>A(p.Ser1397Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00054 in 980,306 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00061 ( 0 hom. )

Consequence

MAGI2
NM_012301.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.447

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07521048).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGI2	NM_012301.4 linkuse as main transcript	c.4190G>A	p.Ser1397Asn	missense_variant	22/22	ENST00000354212.9	NP_036433.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGI2	ENST00000354212.9 linkuse as main transcript	c.4190G>A	p.Ser1397Asn	missense_variant	22/22	1	NM_012301.4	ENSP00000346151	P4	Q86UL8-1

Frequencies

GnomAD3 genomes

AF:

0.000165

AC:

AN:

145640

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000245

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000204

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000290

Gnomad OTH

AF:

0.000499

GnomAD4 exome

AF:

0.000605

AC:

505

AN:

834666

Hom.:

Cov.:

AF XY:

0.000617

AC XY:

238

AN XY:

385736

show subpopulations

Gnomad4 AFR exome

AF:

0.000190

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000645

Gnomad4 OTH exome

AF:

0.000366

GnomAD4 genome

AF:

0.000165

AC:

AN:

145640

Hom.:

Cov.:

AF XY:

0.000141

AC XY:

AN XY:

70798

show subpopulations

Gnomad4 AFR

AF:

0.0000245

Gnomad4 AMR

AF:

0.000204

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000290

Gnomad4 OTH

AF:

0.000499

Alfa

AF:

0.000427

Hom.:

Bravo

AF:

0.000204

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 07, 2022

The c.4190G>A (p.S1397N) alteration is located in exon 22 (coding exon 22) of the MAGI2 gene. This alteration results from a G to A substitution at nucleotide position 4190, causing the serine (S) at amino acid position 1397 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.79

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.061

T;T;.;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.063

LIST_S2

Benign

0.31

T;T;T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.075

T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.0

.;N;.;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

0.13

.;N;N;.

REVEL

Benign

0.043

Sift

Benign

0.53

.;T;T;.

Sift4G

Benign

0.48

T;T;T;T

Polyphen

0.0

.;B;B;.

Vest4

0.12, 0.097

MutPred

0.24

.;Loss of glycosylation at S1397 (P = 9e-04);.;.;

MVP

0.16

MPC

1.0

ClinPred

0.066

GERP RS

-3.7

Varity_R

0.042

gMVP

0.11

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