rs1159145

Variant names:

• chr7-78835841-A-C
• rs1159145
• NM_012301.4:c.418+171249T>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.418+171249T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0932 in 152,270 control chromosomes in the GnomAD database, including 775 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 0.093 (775 hom., cov: 32)
• Consequence: MAGI2 NM_012301.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.637
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGI2	NM_012301.4	c.418+171249T>G		intron_variant	Intron 2 of 21	ENST00000354212.9	NP_036433.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGI2	ENST00000354212.9	c.418+171249T>G		intron_variant	Intron 2 of 21	1	NM_012301.4	ENSP00000346151.4
MAGI2	ENST00000419488.5	c.418+171249T>G		intron_variant	Intron 2 of 20	1		ENSP00000405766.1
MAGI2	ENST00000522391.3	c.418+171249T>G		intron_variant	Intron 2 of 22	5		ENSP00000428389.1
MAGI2	ENST00000637441.1	c.418+171249T>G		intron_variant	Intron 2 of 20	5		ENSP00000489633.1

Frequencies

GnomAD3 genomes AF: 0.0933 AC: 14202 AN: 152152 Hom.: 778 Cov.: 32

Gnomad AFR AF: 0.0384

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0790

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.0214

Gnomad SAS AF: 0.0418

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.162

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.103

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

GnomAD4 genome AF: 0.0932 AC: 14196 AN: 152270 Hom.: 775 Cov.: 32 AF XY: 0.0912 AC XY: 6793 AN XY: 74452

African (AFR) AF: 0.0384 AC: 1598 AN: 41564

American (AMR) AF: 0.0788 AC: 1206 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 362 AN: 3470

East Asian (EAS) AF: 0.0212 AC: 110 AN: 5180

South Asian (SAS) AF: 0.0414 AC: 200 AN: 4830

European-Finnish (FIN) AF: 0.129 AC: 1362 AN: 10596

Middle Eastern (MID) AF: 0.151 AC: 44 AN: 292

European-Non Finnish (NFE) AF: 0.133 AC: 9063 AN: 68016

Other (OTH) AF: 0.102 AC: 216 AN: 2112

Alfa AF: 0.119 Hom.: 665

Bravo AF: 0.0890

Asia WGS AF: 0.0400 AC: 140 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.5
DANN	Benign	0.57
PhyloP100		0.64
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: rs1159145; hg19: chr7-78465157;