rs6962966

Variant names:

• chr7-78174806-A-G
• rs6962966
• NM_012301.4:c.2403+3205T>C

Variant summary

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

The NM_012301.4(MAGI2):​c.2403+3205T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 152,016 control chromosomes in the GnomAD database, including 19,539 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 0.51 (19539 hom., cov: 31)
• Consequence: MAGI2 NM_012301.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0610
• Publications: 11 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGI2	NM_012301.4	c.2403+3205T>C		intron_variant	Intron 14 of 21	ENST00000354212.9	NP_036433.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGI2	ENST00000354212.9	c.2403+3205T>C		intron_variant	Intron 14 of 21	1	NM_012301.4	ENSP00000346151.4

Frequencies

GnomAD3 genomes AF: 0.505 AC: 76745 AN: 151898 Hom.: 19522 Cov.: 31

Gnomad AFR AF: 0.474

Gnomad AMI AF: 0.549

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.577

Gnomad EAS AF: 0.648

Gnomad SAS AF: 0.532

Gnomad FIN AF: 0.601

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.511

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

GnomAD4 genome AF: 0.505 AC: 76811 AN: 152016 Hom.: 19539 Cov.: 31 AF XY: 0.513 AC XY: 38092 AN XY: 74310

African (AFR) AF: 0.475 AC: 19674 AN: 41458

American (AMR) AF: 0.485 AC: 7398 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.577 AC: 2002 AN: 3472

East Asian (EAS) AF: 0.648 AC: 3340 AN: 5154

South Asian (SAS) AF: 0.533 AC: 2564 AN: 4812

European-Finnish (FIN) AF: 0.601 AC: 6354 AN: 10578

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.497 AC: 33750 AN: 67964

Other (OTH) AF: 0.509 AC: 1076 AN: 2114

Alfa AF: 0.509 Hom.: 2465

Bravo AF: 0.495

Asia WGS AF: 0.564 AC: 1958 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	4.0
DANN	Benign	0.52
PhyloP100		0.061
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: rs6962966; hg19: chr7-77804123;