rs11525066

Variant names:

• chr7-78546660-G-A
• rs11525066
• NM_012301.4:c.539-25015C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-78546660-G-A
• chr7-78546660-G-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.539-25015C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0675 in 139,588 control chromosomes in the GnomAD database, including 386 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 0.067 (386 hom., cov: 32)
• Consequence: MAGI2 NM_012301.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.296
• Publications: 8 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0929 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGI2	NM_012301.4	c.539-25015C>T		intron_variant	Intron 3 of 21	ENST00000354212.9	NP_036433.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGI2	ENST00000354212.9	c.539-25015C>T		intron_variant	Intron 3 of 21	1	NM_012301.4	ENSP00000346151.4

Frequencies

GnomAD3 genomes AF: 0.0675 AC: 9420 AN: 139480 Hom.: 385 Cov.: 32

Gnomad AFR AF: 0.0189

Gnomad AMI AF: 0.0135

Gnomad AMR AF: 0.0706

Gnomad ASJ AF: 0.0824

Gnomad EAS AF: 0.0321

Gnomad SAS AF: 0.0717

Gnomad FIN AF: 0.0745

Gnomad MID AF: 0.0588

Gnomad NFE AF: 0.0949

Gnomad OTH AF: 0.0807

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

GnomAD4 genome AF: 0.0675 AC: 9421 AN: 139588 Hom.: 386 Cov.: 32 AF XY: 0.0662 AC XY: 4465 AN XY: 67464

African (AFR) AF: 0.0189 AC: 691 AN: 36654

American (AMR) AF: 0.0706 AC: 927 AN: 13136

Ashkenazi Jewish (ASJ) AF: 0.0824 AC: 277 AN: 3360

East Asian (EAS) AF: 0.0320 AC: 144 AN: 4506

South Asian (SAS) AF: 0.0726 AC: 294 AN: 4050

European-Finnish (FIN) AF: 0.0745 AC: 701 AN: 9412

Middle Eastern (MID) AF: 0.0594 AC: 17 AN: 286

European-Non Finnish (NFE) AF: 0.0949 AC: 6207 AN: 65398

Other (OTH) AF: 0.0796 AC: 151 AN: 1896

Alfa AF: 0.0807 Hom.: 1935

Bravo AF: 0.0608

Asia WGS AF: 0.0420 AC: 147 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.9
DANN	Benign	0.60
PhyloP100		-0.30
Mutation Taster		=99/1	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: rs11525066; hg19: chr7-78175977;