7-78245371-C-T

Variant names:

• chr7-78245371-C-T
• rs798356
• NM_012301.4:c.2047+10572G>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.2047+10572G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 152,164 control chromosomes in the GnomAD database, including 25,876 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 0.55 (25876 hom., cov: 33)
• Consequence: MAGI2 NM_012301.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.218
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.83 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGI2	NM_012301.4	c.2047+10572G>A		intron_variant	Intron 10 of 21	ENST00000354212.9	NP_036433.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGI2	ENST00000354212.9	c.2047+10572G>A		intron_variant	Intron 10 of 21	1	NM_012301.4	ENSP00000346151.4

Frequencies

GnomAD3 genomes AF: 0.547 AC: 83223 AN: 152046 Hom.: 25804 Cov.: 33

Gnomad AFR AF: 0.837

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.546

Gnomad EAS AF: 0.743

Gnomad SAS AF: 0.671

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.510

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

GnomAD4 genome AF: 0.548 AC: 83360 AN: 152164 Hom.: 25876 Cov.: 33 AF XY: 0.551 AC XY: 41009 AN XY: 74366

African (AFR) AF: 0.838 AC: 34805 AN: 41540

American (AMR) AF: 0.435 AC: 6646 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.546 AC: 1896 AN: 3472

East Asian (EAS) AF: 0.743 AC: 3848 AN: 5176

South Asian (SAS) AF: 0.670 AC: 3234 AN: 4826

European-Finnish (FIN) AF: 0.415 AC: 4384 AN: 10560

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.397 AC: 26990 AN: 67990

Other (OTH) AF: 0.517 AC: 1090 AN: 2110

Alfa AF: 0.450 Hom.: 43948

Bravo AF: 0.557

Asia WGS AF: 0.727 AC: 2525 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	4.2
DANN	Benign	0.40
PhyloP100		0.22
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: rs798356; hg19: chr7-77874688;