7-78519747-T-C

Variant names:

• chr7-78519747-T-C
• rs725555
• NM_012301.4:c.754+1683A>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.754+1683A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 152,118 control chromosomes in the GnomAD database, including 3,180 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 0.20 (3180 hom., cov: 32)
• Consequence: MAGI2 NM_012301.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0180
• Publications: 3 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012301.4. 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.754+1683A>G		intron	N/A	NP_036433.2
	MAGI2	NM_001301128.2		c.754+1683A>G		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.754+1683A>G		intron	N/A	ENSP00000346151.4
	MAGI2	ENST00000419488.5	TSL:1	c.754+1683A>G		intron	N/A	ENSP00000405766.1
	MAGI2	ENST00000522391.3	TSL:5	c.754+1683A>G		intron	N/A	ENSP00000428389.1

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30073 AN: 152000 Hom.: 3174 Cov.: 32

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.197

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

GnomAD4 genome AF: 0.198 AC: 30104 AN: 152118 Hom.: 3180 Cov.: 32 AF XY: 0.195 AC XY: 14481 AN XY: 74366

African (AFR) AF: 0.219 AC: 9100 AN: 41508

American (AMR) AF: 0.151 AC: 2309 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 869 AN: 3468

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5178

South Asian (SAS) AF: 0.101 AC: 490 AN: 4828

European-Finnish (FIN) AF: 0.240 AC: 2539 AN: 10564

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.208 AC: 14136 AN: 67980

Other (OTH) AF: 0.195 AC: 412 AN: 2112

Alfa AF: 0.200 Hom.: 2362

Bravo AF: 0.193

Asia WGS AF: 0.0650 AC: 225 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.4
DANN	Benign	0.81
PhyloP100		0.018
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: rs725555; hg19: chr7-78149064;