rs246462

Variant names:

• chr7-78813858-A-G
• rs246462
• NM_012301.4:c.419-186619T>C

Your query was ambiguous. Multiple possible variants found:

• chr7-78813858-A-G
• chr7-78813858-A-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.419-186619T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 150,728 control chromosomes in the GnomAD database, including 8,196 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 0.32 (8196 hom., cov: 29)
• Consequence: MAGI2 NM_012301.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.599
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGI2	NM_012301.4	c.419-186619T>C		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.419-186619T>C		intron_variant	Intron 2 of 21	1	NM_012301.4	ENSP00000346151.4
MAGI2	ENST00000419488.5	c.419-186619T>C		intron_variant	Intron 2 of 20	1		ENSP00000405766.1
MAGI2	ENST00000522391.3	c.419-186619T>C		intron_variant	Intron 2 of 22	5		ENSP00000428389.1
MAGI2	ENST00000637441.1	c.419-186619T>C		intron_variant	Intron 2 of 20	5		ENSP00000489633.1

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47578 AN: 150618 Hom.: 8199 Cov.: 29

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.519

Gnomad SAS AF: 0.327

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.341

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.328

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

GnomAD4 genome AF: 0.316 AC: 47578 AN: 150728 Hom.: 8196 Cov.: 29 AF XY: 0.314 AC XY: 23087 AN XY: 73478

African (AFR) AF: 0.184 AC: 7570 AN: 41140

American (AMR) AF: 0.295 AC: 4461 AN: 15100

Ashkenazi Jewish (ASJ) AF: 0.367 AC: 1274 AN: 3470

East Asian (EAS) AF: 0.520 AC: 2625 AN: 5052

South Asian (SAS) AF: 0.325 AC: 1562 AN: 4800

European-Finnish (FIN) AF: 0.336 AC: 3381 AN: 10068

Middle Eastern (MID) AF: 0.346 AC: 101 AN: 292

European-Non Finnish (NFE) AF: 0.378 AC: 25644 AN: 67802

Other (OTH) AF: 0.329 AC: 689 AN: 2092

Alfa AF: 0.341 Hom.: 1526

Bravo AF: 0.314

Asia WGS AF: 0.394 AC: 1368 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.6
DANN	Benign	0.77
PhyloP100		-0.60
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: rs246462; hg19: chr7-78443174;