rs1009524

Positions:

• chr7-78160086-A-G

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.2784T>C​(p.Asn928=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 1,607,866 control chromosomes in the GnomAD database, including 8,828 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (983 hom., cov: 32)
  • Exomes 𝑓: 0.10 (7845 hom.)
• Consequence: MAGI2 NM_012301.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.772

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=-0.56).
• BP6: Variant 7-78160086-A-G is Benign according to our data. Variant chr7-78160086-A-G is described in ClinVar as [Benign]. Clinvar id is 129563.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.772 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAGI2	NM_012301.4	c.2784T>C	p.Asn928=	synonymous_variant	16/22	ENST00000354212.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAGI2	ENST00000354212.9	c.2784T>C	p.Asn928=	synonymous_variant	16/22	1	NM_012301.4	P4

Frequencies

GnomAD3 genomes AF: 0.112 AC: 16994 AN: 152136 Hom.: 982 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.0832

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0982

Gnomad OTH AF: 0.108

GnomAD3 exomes AF: 0.119 AC: 29574 AN: 248480 Hom.: 1917 AF XY: 0.115 AC XY: 15398 AN XY: 134200

Gnomad AFR exome AF: 0.117

Gnomad AMR exome AF: 0.174

Gnomad ASJ exome AF: 0.150

Gnomad EAS exome AF: 0.180

Gnomad SAS exome AF: 0.0873

Gnomad FIN exome AF: 0.127

Gnomad NFE exome AF: 0.0982

Gnomad OTH exome AF: 0.107

GnomAD4 exome AF: 0.0999 AC: 145450 AN: 1455612 Hom.: 7845 Cov.: 31 AF XY: 0.0997 AC XY: 72070 AN XY: 723206

Gnomad4 AFR exome AF: 0.114

Gnomad4 AMR exome AF: 0.160

Gnomad4 ASJ exome AF: 0.157

Gnomad4 EAS exome AF: 0.181

Gnomad4 SAS exome AF: 0.0879

Gnomad4 FIN exome AF: 0.129

Gnomad4 NFE exome AF: 0.0922

Gnomad4 OTH exome AF: 0.104

GnomAD4 genome AF: 0.112 AC: 17027 AN: 152254 Hom.: 983 Cov.: 32 AF XY: 0.114 AC XY: 8487 AN XY: 74428

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.138

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.171

Gnomad4 SAS AF: 0.0841

Gnomad4 FIN AF: 0.132

Gnomad4 NFE AF: 0.0982

Gnomad4 OTH AF: 0.107

Alfa AF: 0.107 Hom.: 629

Bravo AF: 0.115

Asia WGS AF: 0.116 AC: 401 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 20, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 20, 2019	- -

not specified Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.099
DANN	Benign	0.53

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: rs1009524; hg19: chr7-77789403; COSMIC: COSV62660289;