chr7-78019354-G-C

Position:

• chr7-78019354-G-C

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.Pro1443=) 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/exons	MANE	Protein	UniProt
MAGI2	NM_012301.4	c.4329C>G	p.Pro1443=	synonymous_variant	22/22	ENST00000354212.9	NP_036433.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGI2	ENST00000354212.9	c.4329C>G	p.Pro1443=	synonymous_variant	22/22	1	NM_012301.4	ENSP00000346151	P4

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

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Oct 22, 2013	- -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jul 15, 2024	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. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Mar 01, 2018	- -

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 20, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Nephrotic syndrome 15 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

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;