7-78488899-C-A

Variant names:

• chr7-78488899-C-A
• rs759333
• NM_012301.4:c.1045+862G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012301.4(MAGI2):​c.1045+862G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.657 in 151,804 control chromosomes in the GnomAD database, including 33,243 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 0.66 (33243 hom., cov: 31)
• Consequence: MAGI2 NM_012301.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.21
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.814 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGI2	NM_012301.4	c.1045+862G>T		intron_variant	Intron 6 of 21	ENST00000354212.9	NP_036433.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGI2	ENST00000354212.9	c.1045+862G>T		intron_variant	Intron 6 of 21	1	NM_012301.4	ENSP00000346151.4

Frequencies

GnomAD3 genomes AF: 0.657 AC: 99625 AN: 151686 Hom.: 33191 Cov.: 31

Gnomad AFR AF: 0.718

Gnomad AMI AF: 0.410

Gnomad AMR AF: 0.718

Gnomad ASJ AF: 0.633

Gnomad EAS AF: 0.829

Gnomad SAS AF: 0.835

Gnomad FIN AF: 0.628

Gnomad MID AF: 0.729

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.676

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

GnomAD4 genome AF: 0.657 AC: 99732 AN: 151804 Hom.: 33243 Cov.: 31 AF XY: 0.662 AC XY: 49120 AN XY: 74176

African (AFR) AF: 0.719 AC: 29796 AN: 41446

American (AMR) AF: 0.718 AC: 10930 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.633 AC: 2193 AN: 3464

East Asian (EAS) AF: 0.828 AC: 4255 AN: 5136

South Asian (SAS) AF: 0.836 AC: 4029 AN: 4822

European-Finnish (FIN) AF: 0.628 AC: 6633 AN: 10562

Middle Eastern (MID) AF: 0.726 AC: 212 AN: 292

European-Non Finnish (NFE) AF: 0.588 AC: 39882 AN: 67848

Other (OTH) AF: 0.679 AC: 1429 AN: 2106

Alfa AF: 0.610 Hom.: 54859

Bravo AF: 0.664

Asia WGS AF: 0.816 AC: 2825 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	10
DANN	Benign	0.58
PhyloP100		1.2
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: rs759333; hg19: chr7-78118216; COSMIC: COSV62702591; COSMIC: COSV62702591;