dbSNP rs1990577: MAGI2:c.966-42T>G (chr7-78489882-A-C) – ACMG Classification: Benign (-18 pts)

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_012301.4(MAGI2):c.966-42T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 1,432,782 control chromosomes in the GnomAD database, including 223,275 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 24049 hom., cov: 30)

Exomes 𝑓: 0.55 ( 199226 hom. )

Consequence

MAGI2
NM_012301.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.03

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 7-78489882-A-C is Benign according to our data. Variant chr7-78489882-A-C is described in ClinVar as [Benign]. Clinvar id is 1237001.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGI2	NM_012301.4 link	c.966-42T>G		intron_variant	Intron 5 of 21	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.966-42T>G		intron_variant	Intron 5 of 21	1	NM_012301.4	ENSP00000346151.4		Q86UL8-1

Frequencies

GnomAD3 genomes

AF:

0.571

AC:

84585

AN:

148040

Hom.:

24030

Cov.:

show subpopulations

Gnomad AFR

AF:

0.548

Gnomad AMI

AF:

0.515

Gnomad AMR

AF:

0.655

Gnomad ASJ

AF:

0.536

Gnomad EAS

AF:

0.774

Gnomad SAS

AF:

0.668

Gnomad FIN

AF:

0.594

Gnomad MID

AF:

0.484

Gnomad NFE

AF:

0.544

Gnomad OTH

AF:

0.576

GnomAD3 exomes

AF:

0.606

AC:

133969

AN:

221162

Hom.:

40893

AF XY:

0.601

AC XY:

72085

AN XY:

120026

show subpopulations

Gnomad AFR exome

AF:

0.539

Gnomad AMR exome

AF:

0.751

Gnomad ASJ exome

AF:

0.565

Gnomad EAS exome

AF:

0.774

Gnomad SAS exome

AF:

0.662

Gnomad FIN exome

AF:

0.582

Gnomad NFE exome

AF:

0.546

Gnomad OTH exome

AF:

0.584

GnomAD4 exome

AF:

0.553

AC:

710326

AN:

1284628

Hom.:

199226

Cov.:

AF XY:

0.554

AC XY:

358118

AN XY:

646316

show subpopulations

Gnomad4 AFR exome

AF:

0.526

Gnomad4 AMR exome

AF:

0.725

Gnomad4 ASJ exome

AF:

0.546

Gnomad4 EAS exome

AF:

0.761

Gnomad4 SAS exome

AF:

0.647

Gnomad4 FIN exome

AF:

0.576

Gnomad4 NFE exome

AF:

0.531

Gnomad4 OTH exome

AF:

0.554

GnomAD4 genome

AF:

0.571

AC:

84643

AN:

148154

Hom.:

24049

Cov.:

AF XY:

0.577

AC XY:

41681

AN XY:

72180

show subpopulations

Gnomad4 AFR

AF:

0.548

Gnomad4 AMR

AF:

0.655

Gnomad4 ASJ

AF:

0.536

Gnomad4 EAS

AF:

0.775

Gnomad4 SAS

AF:

0.668

Gnomad4 FIN

AF:

0.594

Gnomad4 NFE

AF:

0.544

Gnomad4 OTH

AF:

0.572

Alfa

AF:

0.531

Hom.:

11951

Bravo

AF:

0.561

Asia WGS

AF:

0.682

AC:

2371

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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:1

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 85% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 79. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.85

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