rs10251504

Variant names:

• chr7-78060571-A-G
• rs10251504
• NM_012301.4:c.3706+18376T>C

Variant summary

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

The NM_012301.4(MAGI2):​c.3706+18376T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 152,136 control chromosomes in the GnomAD database, including 15,310 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 0.45 (15310 hom., cov: 32)
• Consequence: MAGI2 NM_012301.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0500
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012301.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGI2	NM_012301.4	MANE Select	c.3706+18376T>C		intron	N/A	NP_036433.2
	MAGI2	NM_001301128.2		c.3664+18376T>C		intron	N/A	NP_001288057.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGI2	ENST00000354212.9	TSL:1 MANE Select	c.3706+18376T>C		intron	N/A	ENSP00000346151.4
	MAGI2	ENST00000419488.5	TSL:1	c.3664+18376T>C		intron	N/A	ENSP00000405766.1
	MAGI2	ENST00000522391.3	TSL:5	c.3795+5003T>C		intron	N/A	ENSP00000428389.1

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68261 AN: 152020 Hom.: 15317 Cov.: 32

Gnomad AFR AF: 0.467

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.492

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.520

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.395

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.462

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

GnomAD4 genome AF: 0.449 AC: 68274 AN: 152136 Hom.: 15310 Cov.: 32 AF XY: 0.452 AC XY: 33612 AN XY: 74386

African (AFR) AF: 0.467 AC: 19366 AN: 41506

American (AMR) AF: 0.491 AC: 7503 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.366 AC: 1271 AN: 3468

East Asian (EAS) AF: 0.520 AC: 2693 AN: 5176

South Asian (SAS) AF: 0.413 AC: 1993 AN: 4828

European-Finnish (FIN) AF: 0.416 AC: 4405 AN: 10580

Middle Eastern (MID) AF: 0.397 AC: 116 AN: 292

European-Non Finnish (NFE) AF: 0.436 AC: 29668 AN: 67986

Other (OTH) AF: 0.455 AC: 960 AN: 2112

Alfa AF: 0.440 Hom.: 13940

Bravo AF: 0.453

Asia WGS AF: 0.419 AC: 1458 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.8
DANN	Benign	0.60
PhyloP100		0.050
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: rs10251504; hg19: chr7-77689888;