7-78173777-C-T

Variant names:

• chr7-78173777-C-T
• rs2691528
• NM_012301.4:c.2403+4234G>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.2403+4234G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.742 in 151,974 control chromosomes in the GnomAD database, including 41,900 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 0.74 (41900 hom., cov: 30)
• Consequence: MAGI2 NM_012301.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.50
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.75 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGI2	NM_012301.4	c.2403+4234G>A		intron_variant	Intron 14 of 21	ENST00000354212.9	NP_036433.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGI2	ENST00000354212.9	c.2403+4234G>A		intron_variant	Intron 14 of 21	1	NM_012301.4	ENSP00000346151.4

Frequencies

GnomAD3 genomes AF: 0.742 AC: 112694 AN: 151856 Hom.: 41884 Cov.: 30

Gnomad AFR AF: 0.735

Gnomad AMI AF: 0.632

Gnomad AMR AF: 0.752

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.620

Gnomad SAS AF: 0.703

Gnomad FIN AF: 0.782

Gnomad MID AF: 0.682

Gnomad NFE AF: 0.756

Gnomad OTH AF: 0.721

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

GnomAD4 genome AF: 0.742 AC: 112762 AN: 151974 Hom.: 41900 Cov.: 30 AF XY: 0.741 AC XY: 55024 AN XY: 74294

African (AFR) AF: 0.735 AC: 30452 AN: 41440

American (AMR) AF: 0.752 AC: 11486 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.683 AC: 2368 AN: 3468

East Asian (EAS) AF: 0.619 AC: 3190 AN: 5152

South Asian (SAS) AF: 0.702 AC: 3370 AN: 4798

European-Finnish (FIN) AF: 0.782 AC: 8259 AN: 10564

Middle Eastern (MID) AF: 0.668 AC: 195 AN: 292

European-Non Finnish (NFE) AF: 0.755 AC: 51349 AN: 67968

Other (OTH) AF: 0.720 AC: 1519 AN: 2110

Alfa AF: 0.748 Hom.: 62800

Bravo AF: 0.740

Asia WGS AF: 0.678 AC: 2360 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.0040
DANN	Benign	0.43
PhyloP100		-2.5
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: rs2691528; hg19: chr7-77803094;