NM_012301.4:c.3707-383A>G

Variant names:

• chr7-78020359-T-C
• rs2018955
• NM_012301.4:c.3707-383A>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.3707-383A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 152,014 control chromosomes in the GnomAD database, including 5,269 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 0.25 (5269 hom., cov: 31)
• Consequence: MAGI2 NM_012301.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.615
• Publications: 1 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGI2	NM_012301.4	c.3707-383A>G		intron_variant	Intron 21 of 21	ENST00000354212.9	NP_036433.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGI2	ENST00000354212.9	c.3707-383A>G		intron_variant	Intron 21 of 21	1	NM_012301.4	ENSP00000346151.4

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37367 AN: 151896 Hom.: 5266 Cov.: 31

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.555

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.227

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

GnomAD4 genome AF: 0.246 AC: 37401 AN: 152014 Hom.: 5269 Cov.: 31 AF XY: 0.253 AC XY: 18786 AN XY: 74310

African (AFR) AF: 0.291 AC: 12061 AN: 41450

American (AMR) AF: 0.300 AC: 4583 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 706 AN: 3470

East Asian (EAS) AF: 0.555 AC: 2857 AN: 5150

South Asian (SAS) AF: 0.349 AC: 1679 AN: 4816

European-Finnish (FIN) AF: 0.237 AC: 2500 AN: 10564

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.180 AC: 12268 AN: 67972

Other (OTH) AF: 0.230 AC: 485 AN: 2110

Alfa AF: 0.202 Hom.: 1970

Bravo AF: 0.255

Asia WGS AF: 0.450 AC: 1562 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.3
DANN	Benign	0.53
PhyloP100		0.61
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: rs2018955; hg19: chr7-77649676;