7-78836606-A-T

Variant names:

• chr7-78836606-A-T
• rs17454991
• NM_012301.4:c.418+170484T>A

Variant summary

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

The NM_012301.4(MAGI2):​c.418+170484T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 152,048 control chromosomes in the GnomAD database, including 8,995 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 0.33 (8995 hom., cov: 33)
• Consequence: MAGI2 NM_012301.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.109
• Publications: 1 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.691 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGI2	NM_012301.4	c.418+170484T>A		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.418+170484T>A		intron_variant	Intron 2 of 21	1	NM_012301.4	ENSP00000346151.4
MAGI2	ENST00000419488.5	c.418+170484T>A		intron_variant	Intron 2 of 20	1		ENSP00000405766.1
MAGI2	ENST00000522391.3	c.418+170484T>A		intron_variant	Intron 2 of 22	5		ENSP00000428389.1
MAGI2	ENST00000637441.1	c.418+170484T>A		intron_variant	Intron 2 of 20	5		ENSP00000489633.1

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50432 AN: 151930 Hom.: 8995 Cov.: 33

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.710

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.350

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

GnomAD4 genome AF: 0.332 AC: 50458 AN: 152048 Hom.: 8995 Cov.: 33 AF XY: 0.338 AC XY: 25088 AN XY: 74312

African (AFR) AF: 0.252 AC: 10439 AN: 41506

American (AMR) AF: 0.356 AC: 5439 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 1373 AN: 3472

East Asian (EAS) AF: 0.710 AC: 3667 AN: 5164

South Asian (SAS) AF: 0.302 AC: 1454 AN: 4820

European-Finnish (FIN) AF: 0.442 AC: 4661 AN: 10544

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.327 AC: 22190 AN: 67962

Other (OTH) AF: 0.349 AC: 735 AN: 2104

Alfa AF: 0.319 Hom.: 1002

Bravo AF: 0.330

Asia WGS AF: 0.456 AC: 1587 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.2
DANN	Benign	0.34
PhyloP100		0.11
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: rs17454991; hg19: chr7-78465922;