Variant rs117054456 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_012301.4(MAGI2):c.3915G>A(p.Gln1305=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.035 in 1,612,638 control chromosomes in the GnomAD database, including 1,238 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 79 hom., cov: 30)

Exomes 𝑓: 0.036 ( 1159 hom. )

Consequence

MAGI2
NM_012301.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.30

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 Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.29).

BP6

Variant 7-78019768-C-T is Benign according to our data. Variant chr7-78019768-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 95512.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-78019768-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=2.3 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0251 (3807/151934) while in subpopulation NFE AF= 0.0409 (2779/67902). AF 95% confidence interval is 0.0397. There are 79 homozygotes in gnomad4. There are 1748 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 79 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAGI2	NM_012301.4 linkuse as main transcript	c.3915G>A	p.Gln1305=	synonymous_variant	22/22	ENST00000354212.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAGI2	ENST00000354212.9 linkuse as main transcript	c.3915G>A	p.Gln1305=	synonymous_variant	22/22	1	NM_012301.4	P4	Q86UL8-1

Frequencies

GnomAD3 genomes

AF:

0.0251

AC:

3809

AN:

151822

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00814

Gnomad AMI

AF:

0.0471

Gnomad AMR

AF:

0.0223

Gnomad ASJ

AF:

0.0208

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00973

Gnomad FIN

AF:

0.0110

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0409

Gnomad OTH

AF:

0.0297

GnomAD3 exomes

AF:

0.0252

AC:

6243

AN:

247638

Hom.:

124

AF XY:

0.0256

AC XY:

3435

AN XY:

134092

show subpopulations

Gnomad AFR exome

AF:

0.00842

Gnomad AMR exome

AF:

0.0170

Gnomad ASJ exome

AF:

0.0202

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.00951

Gnomad FIN exome

AF:

0.0118

Gnomad NFE exome

AF:

0.0416

Gnomad OTH exome

AF:

0.0261

GnomAD4 exome

AF:

0.0360

AC:

52650

AN:

1460704

Hom.:

1159

Cov.:

AF XY:

0.0355

AC XY:

25801

AN XY:

726516

show subpopulations

Gnomad4 AFR exome

AF:

0.00687

Gnomad4 AMR exome

AF:

0.0168

Gnomad4 ASJ exome

AF:

0.0208

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0101

Gnomad4 FIN exome

AF:

0.0116

Gnomad4 NFE exome

AF:

0.0429

Gnomad4 OTH exome

AF:

0.0304

GnomAD4 genome

AF:

0.0251

AC:

3807

AN:

151934

Hom.:

Cov.:

AF XY:

0.0235

AC XY:

1748

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.00812

Gnomad4 AMR

AF:

0.0222

Gnomad4 ASJ

AF:

0.0208

Gnomad4 EAS

AF:

0.000195

Gnomad4 SAS

AF:

0.00974

Gnomad4 FIN

AF:

0.0110

Gnomad4 NFE

AF:

0.0409

Gnomad4 OTH

AF:

0.0294

Alfa

AF:

0.0312

Hom.:

Bravo

AF:

0.0257

EpiCase

AF:

0.0402

EpiControl

AF:

0.0457

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Sep 05, 2012	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jan 30, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jun 29, 2017	- -

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 14, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 25, 2024	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Benign

0.96

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