7-78685233-G-C

Variant names:

• chr7-78685233-G-C
• rs321967
• NM_012301.4:c.419-57994C>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.419-57994C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.744 in 152,052 control chromosomes in the GnomAD database, including 42,307 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 0.74 (42307 hom., cov: 32)
• Consequence: MAGI2 NM_012301.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.601
• 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=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.946 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGI2	NM_012301.4	c.419-57994C>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.419-57994C>G		intron_variant	Intron 2 of 21	1	NM_012301.4	ENSP00000346151.4

Frequencies

GnomAD3 genomes AF: 0.744 AC: 113081 AN: 151934 Hom.: 42268 Cov.: 32

Gnomad AFR AF: 0.723

Gnomad AMI AF: 0.677

Gnomad AMR AF: 0.772

Gnomad ASJ AF: 0.698

Gnomad EAS AF: 0.969

Gnomad SAS AF: 0.732

Gnomad FIN AF: 0.694

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.746

Gnomad OTH AF: 0.756

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

GnomAD4 genome AF: 0.744 AC: 113173 AN: 152052 Hom.: 42307 Cov.: 32 AF XY: 0.745 AC XY: 55380 AN XY: 74322

African (AFR) AF: 0.723 AC: 29968 AN: 41466

American (AMR) AF: 0.772 AC: 11788 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.698 AC: 2421 AN: 3468

East Asian (EAS) AF: 0.969 AC: 5010 AN: 5172

South Asian (SAS) AF: 0.732 AC: 3526 AN: 4818

European-Finnish (FIN) AF: 0.694 AC: 7327 AN: 10562

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.746 AC: 50700 AN: 67980

Other (OTH) AF: 0.758 AC: 1600 AN: 2112

Alfa AF: 0.742 Hom.: 4960

Bravo AF: 0.751

Asia WGS AF: 0.845 AC: 2938 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	5.0
DANN	Benign	0.75
PhyloP100		-0.60
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: rs321967; hg19: chr7-78314549;