NM_012301.4:c.3568-3354G>A

Variant names:

• chr7-78082439-C-T
• rs3779312
• NM_012301.4:c.3568-3354G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012301.4(MAGI2):​c.3568-3354G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 152,040 control chromosomes in the GnomAD database, including 2,392 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.17 (2392 hom., cov: 31)
• Consequence: MAGI2 NM_012301.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• nephrotic syndrome 15

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• familial idiopathic steroid-resistant nephrotic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: LIMITED Submitted by: G2P
• epilepsy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGI2	NM_012301.4	c.3568-3354G>A		intron_variant	Intron 20 of 21	ENST00000354212.9	NP_036433.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGI2	ENST00000354212.9	c.3568-3354G>A		intron_variant	Intron 20 of 21	1	NM_012301.4	ENSP00000346151.4

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26149 AN: 151922 Hom.: 2389 Cov.: 31

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.165

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.178

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.172 AC: 26169 AN: 152040 Hom.: 2392 Cov.: 31 AF XY: 0.174 AC XY: 12934 AN XY: 74332

African (AFR) AF: 0.114 AC: 4738 AN: 41466

American (AMR) AF: 0.171 AC: 2615 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 749 AN: 3468

East Asian (EAS) AF: 0.141 AC: 725 AN: 5148

South Asian (SAS) AF: 0.237 AC: 1140 AN: 4814

European-Finnish (FIN) AF: 0.209 AC: 2208 AN: 10582

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.198 AC: 13435 AN: 67964

Other (OTH) AF: 0.178 AC: 376 AN: 2112

Alfa AF: 0.187 Hom.: 4078

Bravo AF: 0.164

Asia WGS AF: 0.215 AC: 749 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.6
DANN	Benign	0.46
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3779312; hg19: chr7-77711756;