7-78506875-T-C

Variant names:

• chr7-78506875-T-C
• rs2110630
• NM_012301.4:c.755-5088A>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.755-5088A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.689 in 152,170 control chromosomes in the GnomAD database, including 36,911 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 0.69 (36911 hom., cov: 32)
• Consequence: MAGI2 NM_012301.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.64
• 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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.836 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGI2	NM_012301.4	MANE Select	c.755-5088A>G		intron	N/A	NP_036433.2
	MAGI2	NM_001301128.2		c.755-5088A>G		intron	N/A	NP_001288057.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGI2	ENST00000354212.9	TSL:1 MANE Select	c.755-5088A>G		intron	N/A	ENSP00000346151.4
	MAGI2	ENST00000419488.5	TSL:1	c.755-5088A>G		intron	N/A	ENSP00000405766.1
	MAGI2	ENST00000522391.3	TSL:5	c.755-5088A>G		intron	N/A	ENSP00000428389.1

Frequencies

GnomAD3 genomes AF: 0.689 AC: 104690 AN: 152052 Hom.: 36857 Cov.: 32

Gnomad AFR AF: 0.843

Gnomad AMI AF: 0.595

Gnomad AMR AF: 0.597

Gnomad ASJ AF: 0.687

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.732

Gnomad FIN AF: 0.617

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.642

Gnomad OTH AF: 0.674

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

GnomAD4 genome AF: 0.689 AC: 104802 AN: 152170 Hom.: 36911 Cov.: 32 AF XY: 0.686 AC XY: 50988 AN XY: 74380

African (AFR) AF: 0.843 AC: 35038 AN: 41556

American (AMR) AF: 0.597 AC: 9120 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.687 AC: 2384 AN: 3470

East Asian (EAS) AF: 0.467 AC: 2420 AN: 5178

South Asian (SAS) AF: 0.732 AC: 3527 AN: 4820

European-Finnish (FIN) AF: 0.617 AC: 6516 AN: 10560

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.642 AC: 43623 AN: 67982

Other (OTH) AF: 0.673 AC: 1425 AN: 2116

Alfa AF: 0.656 Hom.: 90445

Bravo AF: 0.686

Asia WGS AF: 0.645 AC: 2244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.029
DANN	Benign	0.49
PhyloP100		-1.6
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: rs2110630; hg19: chr7-78136192;