7-78019414-C-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.4269G>C(p.Pro1423=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 1,128,038 control chromosomes in the GnomAD database, including 30,428 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (6856 hom., cov: 29)
  • Exomes 𝑓: 0.21 (23572 hom.)
• Consequence: MAGI2 NM_012301.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.15

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=-0.74).
• BP6: Variant 7-78019414-C-G is Benign according to our data. Variant chr7-78019414-C-G is described in ClinVar as [Benign]. Clinvar id is 95513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-78019414-C-G is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-1.15 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAGI2	NM_012301.4	c.4269G>C	p.Pro1423=	synonymous_variant	22/22	ENST00000354212.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAGI2	ENST00000354212.9	c.4269G>C	p.Pro1423=	synonymous_variant	22/22	1	NM_012301.4	P4

Frequencies

GnomAD3 genomes AF: 0.283 AC: 41184 AN: 145556 Hom.: 6851 Cov.: 29

Gnomad AFR AF: 0.404

Gnomad AMI AF: 0.210

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.561

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.265

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.253

GnomAD3 exomes AF: 0.349 AC: 259 AN: 742 Hom.: 32 AF XY: 0.362 AC XY: 178 AN XY: 492

Gnomad AFR exome AF: 0.500

Gnomad AMR exome AF: 0.569

Gnomad ASJ exome AF: 0.313

Gnomad EAS exome AF: 0.500

Gnomad SAS exome AF: 0.508

Gnomad FIN exome AF: 0.324

Gnomad NFE exome AF: 0.269

Gnomad OTH exome AF: 0.458

GnomAD4 exome AF: 0.205 AC: 201647 AN: 982416 Hom.: 23572 Cov.: 30 AF XY: 0.205 AC XY: 95060 AN XY: 462686

Gnomad4 AFR exome AF: 0.420

Gnomad4 AMR exome AF: 0.373

Gnomad4 ASJ exome AF: 0.277

Gnomad4 EAS exome AF: 0.593

Gnomad4 SAS exome AF: 0.338

Gnomad4 FIN exome AF: 0.226

Gnomad4 NFE exome AF: 0.185

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.283 AC: 41214 AN: 145622 Hom.: 6856 Cov.: 29 AF XY: 0.288 AC XY: 20434 AN XY: 70856

Gnomad4 AFR AF: 0.404

Gnomad4 AMR AF: 0.309

Gnomad4 ASJ AF: 0.273

Gnomad4 EAS AF: 0.560

Gnomad4 SAS AF: 0.353

Gnomad4 FIN AF: 0.243

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.255

Alfa AF: 0.238 Hom.: 619

Bravo AF: 0.295

Asia WGS AF: 0.438 AC: 1421 AN: 3254

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 22, 2013	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Mar 01, 2018	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 20, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	5.9
Dann	Benign	0.82

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: rs2960452; hg19: chr7-77648731; COSMIC: COSV62634115; COSMIC: COSV62634115;