7-78081618-T-C

Variant names:

• chr7-78081618-T-C
• rs4727608
• NM_012301.4:c.3568-2533A>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.3568-2533A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.674 in 152,006 control chromosomes in the GnomAD database, including 34,799 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 0.67 (34799 hom., cov: 31)
• Consequence: MAGI2 NM_012301.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.202
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGI2	NM_012301.4	c.3568-2533A>G		intron_variant	Intron 20 of 21	ENST00000354212.9	NP_036433.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGI2	ENST00000354212.9	c.3568-2533A>G		intron_variant	Intron 20 of 21	1	NM_012301.4	ENSP00000346151.4

Frequencies

GnomAD3 genomes AF: 0.674 AC: 102446 AN: 151888 Hom.: 34769 Cov.: 31

Gnomad AFR AF: 0.738

Gnomad AMI AF: 0.730

Gnomad AMR AF: 0.655

Gnomad ASJ AF: 0.727

Gnomad EAS AF: 0.751

Gnomad SAS AF: 0.678

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.647

Gnomad OTH AF: 0.669

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

GnomAD4 genome AF: 0.674 AC: 102526 AN: 152006 Hom.: 34799 Cov.: 31 AF XY: 0.673 AC XY: 49990 AN XY: 74258

African (AFR) AF: 0.738 AC: 30587 AN: 41462

American (AMR) AF: 0.654 AC: 9985 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.727 AC: 2522 AN: 3470

East Asian (EAS) AF: 0.751 AC: 3877 AN: 5160

South Asian (SAS) AF: 0.679 AC: 3272 AN: 4820

European-Finnish (FIN) AF: 0.574 AC: 6056 AN: 10542

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.647 AC: 43963 AN: 67976

Other (OTH) AF: 0.665 AC: 1404 AN: 2112

Alfa AF: 0.654 Hom.: 25163

Bravo AF: 0.684

Asia WGS AF: 0.700 AC: 2434 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.8
DANN	Benign	0.43
PhyloP100		-0.20
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: rs4727608; hg19: chr7-77710935;