NM_012301.4:c.1103+3041T>G

Variant names:

• chr7-78366115-A-C
• rs9640699
• NM_012301.4:c.1103+3041T>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.1103+3041T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 151,998 control chromosomes in the GnomAD database, including 25,648 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 0.58 (25648 hom., cov: 32)
• Consequence: MAGI2 NM_012301.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.353
• Publications: 4 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGI2	NM_012301.4	c.1103+3041T>G		intron_variant	Intron 7 of 21	ENST00000354212.9	NP_036433.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGI2	ENST00000354212.9	c.1103+3041T>G		intron_variant	Intron 7 of 21	1	NM_012301.4	ENSP00000346151.4

Frequencies

GnomAD3 genomes AF: 0.575 AC: 87394 AN: 151880 Hom.: 25636 Cov.: 32

Gnomad AFR AF: 0.527

Gnomad AMI AF: 0.645

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.690

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.531

Gnomad FIN AF: 0.627

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.620

Gnomad OTH AF: 0.579

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

GnomAD4 genome AF: 0.575 AC: 87436 AN: 151998 Hom.: 25648 Cov.: 32 AF XY: 0.571 AC XY: 42442 AN XY: 74274

African (AFR) AF: 0.527 AC: 21857 AN: 41458

American (AMR) AF: 0.525 AC: 8021 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.690 AC: 2396 AN: 3472

East Asian (EAS) AF: 0.360 AC: 1857 AN: 5164

South Asian (SAS) AF: 0.530 AC: 2555 AN: 4820

European-Finnish (FIN) AF: 0.627 AC: 6622 AN: 10554

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.620 AC: 42136 AN: 67956

Other (OTH) AF: 0.574 AC: 1209 AN: 2106

Alfa AF: 0.600 Hom.: 4154

Bravo AF: 0.563

Asia WGS AF: 0.437 AC: 1521 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.8
DANN	Benign	0.76
PhyloP100		0.35
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: rs9640699; hg19: chr7-77995432;