NM_012301.4:c.419-3147A>G

Variant names:

• chr7-78630386-T-C
• rs38121
• NM_012301.4:c.419-3147A>G

Variant summary

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

The NM_012301.4(MAGI2):​c.419-3147A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 148,668 control chromosomes in the GnomAD database, including 30,151 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 0.63 (30151 hom., cov: 26)
• Consequence: MAGI2 NM_012301.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.613
• Publications: 1 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.838 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012301.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGI2	NM_012301.4	MANE Select	c.419-3147A>G		intron	N/A	NP_036433.2
	MAGI2	NM_001301128.2		c.419-3147A>G		intron	N/A	NP_001288057.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGI2	ENST00000354212.9	TSL:1 MANE Select	c.419-3147A>G		intron	N/A	ENSP00000346151.4
	MAGI2	ENST00000419488.5	TSL:1	c.419-3147A>G		intron	N/A	ENSP00000405766.1
	MAGI2	ENST00000522391.3	TSL:5	c.419-3147A>G		intron	N/A	ENSP00000428389.1

Frequencies

GnomAD3 genomes AF: 0.632 AC: 93836 AN: 148570 Hom.: 30131 Cov.: 26

Gnomad AFR AF: 0.528

Gnomad AMI AF: 0.636

Gnomad AMR AF: 0.668

Gnomad ASJ AF: 0.738

Gnomad EAS AF: 0.859

Gnomad SAS AF: 0.646

Gnomad FIN AF: 0.685

Gnomad MID AF: 0.597

Gnomad NFE AF: 0.655

Gnomad OTH AF: 0.625

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

GnomAD4 genome AF: 0.632 AC: 93906 AN: 148668 Hom.: 30151 Cov.: 26 AF XY: 0.634 AC XY: 45721 AN XY: 72092

African (AFR) AF: 0.528 AC: 21256 AN: 40238

American (AMR) AF: 0.668 AC: 9935 AN: 14862

Ashkenazi Jewish (ASJ) AF: 0.738 AC: 2554 AN: 3460

East Asian (EAS) AF: 0.859 AC: 4312 AN: 5020

South Asian (SAS) AF: 0.646 AC: 3055 AN: 4730

European-Finnish (FIN) AF: 0.685 AC: 6432 AN: 9392

Middle Eastern (MID) AF: 0.595 AC: 169 AN: 284

European-Non Finnish (NFE) AF: 0.655 AC: 44305 AN: 67688

Other (OTH) AF: 0.628 AC: 1309 AN: 2084

Alfa AF: 0.646 Hom.: 47695

Bravo AF: 0.631

Asia WGS AF: 0.755 AC: 2624 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.9
DANN	Benign	0.70
PhyloP100		-0.61
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: rs38121; hg19: chr7-78259702; COSMIC: COSV62679155; COSMIC: COSV62679155;