NM_012301.4:c.1046-20311C>T

Variant names:

• chr7-78389524-G-A
• rs12705417
• NM_012301.4:c.1046-20311C>T

Variant summary

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

The NM_012301.4(MAGI2):​c.1046-20311C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,188 control chromosomes in the GnomAD database, including 2,145 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 0.16 (2145 hom., cov: 33)
• Consequence: MAGI2 NM_012301.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0320
• Publications: 2 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGI2	NM_012301.4	c.1046-20311C>T		intron_variant	Intron 6 of 21	ENST00000354212.9	NP_036433.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGI2	ENST00000354212.9	c.1046-20311C>T		intron_variant	Intron 6 of 21	1	NM_012301.4	ENSP00000346151.4

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24613 AN: 152070 Hom.: 2146 Cov.: 33

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.0504

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.142

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

GnomAD4 genome AF: 0.162 AC: 24621 AN: 152188 Hom.: 2145 Cov.: 33 AF XY: 0.162 AC XY: 12059 AN XY: 74404

African (AFR) AF: 0.151 AC: 6256 AN: 41528

American (AMR) AF: 0.102 AC: 1553 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 763 AN: 3470

East Asian (EAS) AF: 0.0500 AC: 259 AN: 5184

South Asian (SAS) AF: 0.223 AC: 1075 AN: 4818

European-Finnish (FIN) AF: 0.199 AC: 2103 AN: 10580

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.178 AC: 12137 AN: 68010

Other (OTH) AF: 0.141 AC: 297 AN: 2112

Alfa AF: 0.160 Hom.: 358

Bravo AF: 0.152

Asia WGS AF: 0.134 AC: 467 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.7
DANN	Benign	0.86
PhyloP100		0.032
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: rs12705417; hg19: chr7-78018841;