7-78428523-C-T

Variant names:

• chr7-78428523-C-T
• rs10485886
• NM_012301.4:c.1046-59310G>A

Variant summary

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

The ENST00000354212.9(MAGI2):​c.1046-59310G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 152,006 control chromosomes in the GnomAD database, including 6,846 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 0.29 (6846 hom., cov: 32)
• Consequence: MAGI2 ENST00000354212.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.95
• 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

ENSG00000285892 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000354212.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGI2	NM_012301.4	MANE Select	c.1046-59310G>A		intron	N/A	NP_036433.2
	MAGI2	NM_001301128.2		c.1046-59310G>A		intron	N/A	NP_001288057.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGI2	ENST00000354212.9	TSL:1 MANE Select	c.1046-59310G>A		intron	N/A	ENSP00000346151.4
	MAGI2	ENST00000419488.5	TSL:1	c.1046-59310G>A		intron	N/A	ENSP00000405766.1
	MAGI2	ENST00000519748.5	TSL:1	c.-128-59310G>A		intron	N/A	ENSP00000486774.1

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44226 AN: 151886 Hom.: 6824 Cov.: 32

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.0686

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.220

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.276

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

GnomAD4 genome AF: 0.291 AC: 44298 AN: 152006 Hom.: 6846 Cov.: 32 AF XY: 0.286 AC XY: 21212 AN XY: 74288

African (AFR) AF: 0.376 AC: 15575 AN: 41444

American (AMR) AF: 0.229 AC: 3502 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 622 AN: 3468

East Asian (EAS) AF: 0.0692 AC: 358 AN: 5174

South Asian (SAS) AF: 0.169 AC: 816 AN: 4822

European-Finnish (FIN) AF: 0.263 AC: 2780 AN: 10554

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.290 AC: 19692 AN: 67950

Other (OTH) AF: 0.275 AC: 581 AN: 2112

Alfa AF: 0.282 Hom.: 27726

Bravo AF: 0.295

Asia WGS AF: 0.135 AC: 474 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.19
DANN	Benign	0.72
PhyloP100		-1.9
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: rs10485886; hg19: chr7-78057840;