chr7-79453045-G-C

Position:

• chr7-79453045-G-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_012301.4(MAGI2):​c.276C>G​(p.Pro92=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.01 in 1,602,380 control chromosomes in the GnomAD database, including 129 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0060 (2 hom., cov: 32)
  • Exomes 𝑓: 0.010 (127 hom.)
• Consequence: MAGI2 NM_012301.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 1.03

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-AS3 (HGNC:40862): (MAGI2 antisense RNA 3)

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 7-79453045-G-C is Benign according to our data. Variant chr7-79453045-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 95511.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-79453045-G-C is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=1.03 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAGI2	NM_012301.4	c.276C>G	p.Pro92=	synonymous_variant	1/22	ENST00000354212.9
MAGI2-AS3	NR_038346.1	n.89G>C		non_coding_transcript_exon_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAGI2	ENST00000354212.9	c.276C>G	p.Pro92=	synonymous_variant	1/22	1	NM_012301.4	P4
MAGI2-AS3	ENST00000426835.6	n.43G>C		non_coding_transcript_exon_variant	1/4	3

Frequencies

GnomAD3 genomes AF: 0.00597 AC: 909 AN: 152196 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00166

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.00196

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00766

Gnomad FIN AF: 0.00207

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0107

Gnomad OTH AF: 0.00334

GnomAD3 exomes AF: 0.00676 AC: 1635 AN: 242030 Hom.: 14 AF XY: 0.00725 AC XY: 948 AN XY: 130692

Gnomad AFR exome AF: 0.00217

Gnomad AMR exome AF: 0.00142

Gnomad ASJ exome AF: 0.00154

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0106

Gnomad FIN exome AF: 0.00176

Gnomad NFE exome AF: 0.0106

Gnomad OTH exome AF: 0.00664

GnomAD4 exome AF: 0.0105 AC: 15165 AN: 1450066 Hom.: 127 Cov.: 31 AF XY: 0.0103 AC XY: 7424 AN XY: 720146

Gnomad4 AFR exome AF: 0.00126

Gnomad4 AMR exome AF: 0.00143

Gnomad4 ASJ exome AF: 0.00147

Gnomad4 EAS exome AF: 0.0000505

Gnomad4 SAS exome AF: 0.0112

Gnomad4 FIN exome AF: 0.00208

Gnomad4 NFE exome AF: 0.0123

Gnomad4 OTH exome AF: 0.00661

GnomAD4 genome AF: 0.00596 AC: 908 AN: 152314 Hom.: 2 Cov.: 32 AF XY: 0.00549 AC XY: 409 AN XY: 74460

Gnomad4 AFR AF: 0.00166

Gnomad4 AMR AF: 0.00196

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00746

Gnomad4 FIN AF: 0.00207

Gnomad4 NFE AF: 0.0107

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00708 Hom.: 2

Bravo AF: 0.00567

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:4

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2023	MAGI2: BP4, BP7, BS1, BS2; MAGI2-AS3: BS1, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 19, 2020	- -
Likely benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jan 26, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 20, 2023	- -

MAGI2-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 05, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Nov 11, 2013

- -

Nephrotic syndrome 15 Benign:1

Benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Aug 22, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	15
DANN	Benign	0.88
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs146012909; hg19: chr7-79082361;