7-78019354-G-C

Variant names:

• chr7-78019354-G-C
• rs13438302
• NM_012301.4:c.4329C>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.4329C>G​(p.Pro1443Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 1,508,894 control chromosomes in the GnomAD database, including 48,992 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (7847 hom., cov: 30)
  • Exomes 𝑓: 0.23 (41145 hom.)
• Consequence: MAGI2 NM_012301.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.794

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=-0.71).
• BP6: Variant 7-78019354-G-C is Benign according to our data. Variant chr7-78019354-G-C is described in ClinVar as [Benign]. Clinvar id is 95514.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-78019354-G-C is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.794 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGI2	NM_012301.4	c.4329C>G	p.Pro1443Pro	synonymous_variant	Exon 22 of 22	ENST00000354212.9	NP_036433.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGI2	ENST00000354212.9	c.4329C>G	p.Pro1443Pro	synonymous_variant	Exon 22 of 22	1	NM_012301.4	ENSP00000346151.4

Frequencies

GnomAD3 genomes AF: 0.297 AC: 44596 AN: 150236 Hom.: 7836 Cov.: 30

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.640

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.276

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.262

GnomAD3 exomes AF: 0.308 AC: 33794 AN: 109592 Hom.: 6049 AF XY: 0.301 AC XY: 18636 AN XY: 61832

Gnomad AFR exome AF: 0.411

Gnomad AMR exome AF: 0.427

Gnomad ASJ exome AF: 0.277

Gnomad EAS exome AF: 0.639

Gnomad SAS exome AF: 0.351

Gnomad FIN exome AF: 0.253

Gnomad NFE exome AF: 0.193

Gnomad OTH exome AF: 0.268

GnomAD4 exome AF: 0.227 AC: 308509 AN: 1358552 Hom.: 41145 Cov.: 32 AF XY: 0.230 AC XY: 154144 AN XY: 671056

Gnomad4 AFR exome AF: 0.427

Gnomad4 AMR exome AF: 0.399

Gnomad4 ASJ exome AF: 0.278

Gnomad4 EAS exome AF: 0.652

Gnomad4 SAS exome AF: 0.354

Gnomad4 FIN exome AF: 0.248

Gnomad4 NFE exome AF: 0.191

Gnomad4 OTH exome AF: 0.261

GnomAD4 genome AF: 0.297 AC: 44650 AN: 150342 Hom.: 7847 Cov.: 30 AF XY: 0.304 AC XY: 22293 AN XY: 73418

Gnomad4 AFR AF: 0.422

Gnomad4 AMR AF: 0.320

Gnomad4 ASJ AF: 0.277

Gnomad4 EAS AF: 0.639

Gnomad4 SAS AF: 0.373

Gnomad4 FIN AF: 0.274

Gnomad4 NFE AF: 0.191

Gnomad4 OTH AF: 0.264

Alfa AF: 0.154 Hom.: 436

Bravo AF: 0.309

Asia WGS AF: 0.499 AC: 1729 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Oct 22, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 01, 2018

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 51% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 47. Only high quality variants are reported. -

not provided Benign:3

Nov 20, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 01, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nephrotic syndrome 15 Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	5.0
DANN	Benign	0.68

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: rs13438302; hg19: chr7-77648671;