rs319872

Variant names:

• chr7-78600926-A-G
• rs319872
• NM_012301.4:c.538+26194T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_012301.4(MAGI2):​c.538+26194T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 152,042 control chromosomes in the GnomAD database, including 12,153 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 0.38 (12153 hom., cov: 33)
• Consequence: MAGI2 NM_012301.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.84
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGI2	NM_012301.4	c.538+26194T>C		intron_variant	Intron 3 of 21	ENST00000354212.9	NP_036433.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGI2	ENST00000354212.9	c.538+26194T>C		intron_variant	Intron 3 of 21	1	NM_012301.4	ENSP00000346151.4

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57446 AN: 151924 Hom.: 12133 Cov.: 33

Gnomad AFR AF: 0.572

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.344

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

GnomAD4 genome AF: 0.378 AC: 57505 AN: 152042 Hom.: 12153 Cov.: 33 AF XY: 0.365 AC XY: 27099 AN XY: 74338

African (AFR) AF: 0.572 AC: 23720 AN: 41454

American (AMR) AF: 0.264 AC: 4029 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 885 AN: 3464

East Asian (EAS) AF: 0.135 AC: 698 AN: 5182

South Asian (SAS) AF: 0.171 AC: 823 AN: 4824

European-Finnish (FIN) AF: 0.266 AC: 2814 AN: 10590

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.343 AC: 23296 AN: 67948

Other (OTH) AF: 0.341 AC: 720 AN: 2114

Alfa AF: 0.347 Hom.: 19258

Bravo AF: 0.391

Asia WGS AF: 0.161 AC: 560 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	15
DANN	Benign	0.95
PhyloP100		1.8
Mutation Taster		=98/2	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: rs319872; hg19: chr7-78230243; COSMIC: COSV62642297;