Variant rs3735442 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_012301.4(MAGI2):c.1014G>A(p.Lys338Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 1,610,112 control chromosomes in the GnomAD database, including 76,886 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 8564 hom., cov: 32)

Exomes 𝑓: 0.30 ( 68322 hom. )

Consequence

MAGI2
NM_012301.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.67

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 (HGNC:):

MAGI2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 7-78489792-C-T is Benign according to our data. Variant chr7-78489792-C-T is described in ClinVar as [Benign]. Clinvar id is 129557.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.67 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGI2	NM_012301.4 linkuse as main transcript	c.1014G>A	p.Lys338Lys	synonymous_variant	6/22	ENST00000354212.9	NP_036433.2	Q86UL8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGI2	ENST00000354212.9 linkuse as main transcript	c.1014G>A	p.Lys338Lys	synonymous_variant	6/22	1	NM_012301.4	ENSP00000346151.4		Q86UL8-1

Frequencies

GnomAD3 genomes

AF:

0.327

AC:

49520

AN:

151548

Hom.:

8539

Cov.:

show subpopulations

Gnomad AFR

AF:

0.427

Gnomad AMI

AF:

0.110

Gnomad AMR

AF:

0.257

Gnomad ASJ

AF:

0.313

Gnomad EAS

AF:

0.227

Gnomad SAS

AF:

0.295

Gnomad FIN

AF:

0.283

Gnomad MID

AF:

0.399

Gnomad NFE

AF:

0.302

Gnomad OTH

AF:

0.317

GnomAD3 exomes

AF:

0.288

AC:

71929

AN:

249956

Hom.:

10768

AF XY:

0.291

AC XY:

39249

AN XY:

135086

show subpopulations

Gnomad AFR exome

AF:

0.433

Gnomad AMR exome

AF:

0.193

Gnomad ASJ exome

AF:

0.308

Gnomad EAS exome

AF:

0.237

Gnomad SAS exome

AF:

0.302

Gnomad FIN exome

AF:

0.284

Gnomad NFE exome

AF:

0.298

Gnomad OTH exome

AF:

0.304

GnomAD4 exome

AF:

0.303

AC:

442211

AN:

1458446

Hom.:

68322

Cov.:

AF XY:

0.303

AC XY:

219956

AN XY:

725486

show subpopulations

Gnomad4 AFR exome

AF:

0.437

Gnomad4 AMR exome

AF:

0.203

Gnomad4 ASJ exome

AF:

0.309

Gnomad4 EAS exome

AF:

0.239

Gnomad4 SAS exome

AF:

0.301

Gnomad4 FIN exome

AF:

0.289

Gnomad4 NFE exome

AF:

0.305

Gnomad4 OTH exome

AF:

0.314

GnomAD4 genome

AF:

0.327

AC:

49586

AN:

151666

Hom.:

8564

Cov.:

AF XY:

0.324

AC XY:

23974

AN XY:

74082

show subpopulations

Gnomad4 AFR

AF:

0.427

Gnomad4 AMR

AF:

0.257

Gnomad4 ASJ

AF:

0.313

Gnomad4 EAS

AF:

0.227

Gnomad4 SAS

AF:

0.294

Gnomad4 FIN

AF:

0.283

Gnomad4 NFE

AF:

0.302

Gnomad4 OTH

AF:

0.323

Alfa

AF:

0.309

Hom.:

9942

Bravo

AF:

0.329

Asia WGS

AF:

0.290

AC:

1009

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 25, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 20, 2017	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	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. -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jul 15, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 41% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 38. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.81

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