7-78668745-G-C

Variant names:

• chr7-78668745-G-C
• rs321986
• NM_012301.4:c.419-41506C>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.419-41506C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.619 in 150,706 control chromosomes in the GnomAD database, including 29,306 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 0.62 (29306 hom., cov: 28)
• Consequence: MAGI2 NM_012301.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27
• Publications: 10 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 (EAS) allele frequency at 95% confidence interval = 0.892 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGI2	NM_012301.4	c.419-41506C>G		intron_variant	Intron 2 of 21	ENST00000354212.9	NP_036433.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGI2	ENST00000354212.9	c.419-41506C>G		intron_variant	Intron 2 of 21	1	NM_012301.4	ENSP00000346151.4

Frequencies

GnomAD3 genomes AF: 0.618 AC: 93138 AN: 150590 Hom.: 29268 Cov.: 28

Gnomad AFR AF: 0.551

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.665

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.914

Gnomad SAS AF: 0.666

Gnomad FIN AF: 0.632

Gnomad MID AF: 0.510

Gnomad NFE AF: 0.621

Gnomad OTH AF: 0.605

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

GnomAD4 genome AF: 0.619 AC: 93241 AN: 150706 Hom.: 29306 Cov.: 28 AF XY: 0.621 AC XY: 45712 AN XY: 73588

African (AFR) AF: 0.551 AC: 22499 AN: 40810

American (AMR) AF: 0.665 AC: 10055 AN: 15128

Ashkenazi Jewish (ASJ) AF: 0.631 AC: 2182 AN: 3458

East Asian (EAS) AF: 0.914 AC: 4684 AN: 5126

South Asian (SAS) AF: 0.666 AC: 3163 AN: 4752

European-Finnish (FIN) AF: 0.632 AC: 6614 AN: 10462

Middle Eastern (MID) AF: 0.517 AC: 149 AN: 288

European-Non Finnish (NFE) AF: 0.621 AC: 42066 AN: 67708

Other (OTH) AF: 0.609 AC: 1260 AN: 2070

Alfa AF: 0.483 Hom.: 1295

Bravo AF: 0.622

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.47
DANN	Benign	0.41
PhyloP100		-2.3
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: rs321986; hg19: chr7-78298061;