rs34937835

chr7-78256235-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_012301.4(MAGI2):c.1755C>T(p.Pro585=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0172 in 1,614,008 control chromosomes in the GnomAD database, including 385 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (41 hom., cov: 32)
  • Exomes 𝑓: 0.017 (344 hom.)
• Consequence: MAGI2 NM_012301.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.708

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 7-78256235-G-A is Benign according to our data. Variant chr7-78256235-G-A is described in ClinVar as [Benign]. Clinvar id is 95509.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-78256235-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=0.708 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAGI2	NM_012301.4	c.1755C>T	p.Pro585=	synonymous_variant	10/22	ENST00000354212.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAGI2	ENST00000354212.9	c.1755C>T	p.Pro585=	synonymous_variant	10/22	1	NM_012301.4	P4

Frequencies

GnomAD3 genomes AF: 0.0157 AC: 2394 AN: 152168 Hom.: 41 Cov.: 32

Gnomad AFR AF: 0.00277

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0359

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.0422

Gnomad SAS AF: 0.00580

Gnomad FIN AF: 0.0424

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0146

Gnomad OTH AF: 0.0143

GnomAD3 exomes AF: 0.0223 AC: 5590 AN: 250588 Hom.: 109 AF XY: 0.0204 AC XY: 2761 AN XY: 135404

Gnomad AFR exome AF: 0.00295

Gnomad AMR exome AF: 0.0535

Gnomad ASJ exome AF: 0.00358

Gnomad EAS exome AF: 0.0372

Gnomad SAS exome AF: 0.00343

Gnomad FIN exome AF: 0.0474

Gnomad NFE exome AF: 0.0153

Gnomad OTH exome AF: 0.0185

GnomAD4 exome AF: 0.0173 AC: 25342 AN: 1461722 Hom.: 344 Cov.: 32 AF XY: 0.0167 AC XY: 12112 AN XY: 727154

Gnomad4 AFR exome AF: 0.00272

Gnomad4 AMR exome AF: 0.0506

Gnomad4 ASJ exome AF: 0.00298

Gnomad4 EAS exome AF: 0.0532

Gnomad4 SAS exome AF: 0.00354

Gnomad4 FIN exome AF: 0.0480

Gnomad4 NFE exome AF: 0.0154

Gnomad4 OTH exome AF: 0.0139

GnomAD4 genome AF: 0.0157 AC: 2397 AN: 152286 Hom.: 41 Cov.: 32 AF XY: 0.0167 AC XY: 1247 AN XY: 74456

Gnomad4 AFR AF: 0.00277

Gnomad4 AMR AF: 0.0360

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.0423

Gnomad4 SAS AF: 0.00601

Gnomad4 FIN AF: 0.0424

Gnomad4 NFE AF: 0.0146

Gnomad4 OTH AF: 0.0142

Alfa AF: 0.0131 Hom.: 10

Bravo AF: 0.0163

Asia WGS AF: 0.0170 AC: 60 AN: 3478

EpiCase AF: 0.0114

EpiControl AF: 0.0108

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Oct 15, 2012	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	May 09, 2013	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 12, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 20, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
Cadd	Benign	11
Dann	Benign	0.61

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

Other links and lift over

dbSNP: rs34937835; hg19: chr7-77885552;