dbSNP rs10485936: MAGI2:c.302-211540T>G (chr7-79218746-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_012301.4(MAGI2):c.302-211540T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.029 in 152,222 control chromosomes in the GnomAD database, including 100 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 0.029 ( 100 hom., cov: 32)

Consequence

MAGI2
NM_012301.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.592

Publications

1 publications found

Variant links:

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

MAGI2 links:

ENSG00000308242 (HGNC:):

ENSG00000308242 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.029 (4414/152222) while in subpopulation AFR AF = 0.0462 (1916/41468). AF 95% confidence interval is 0.0445. There are 100 homozygotes in GnomAd4. There are 2196 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 100 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGI2	NM_012301.4 link	c.302-211540T>G		intron_variant	Intron 1 of 21	ENST00000354212.9	NP_036433.2	Q86UL8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGI2	ENST00000354212.9 link	c.302-211540T>G		intron_variant	Intron 1 of 21	1	NM_012301.4	ENSP00000346151.4		Q86UL8-1

Frequencies

GnomAD3 genomes

AF:

0.0291

AC:

4420

AN:

152104

Hom.:

100

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0463

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0168

Gnomad ASJ

AF:

0.0251

Gnomad EAS

AF:

0.0399

Gnomad SAS

AF:

0.0205

Gnomad FIN

AF:

0.0459

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0189

Gnomad OTH

AF:

0.0320

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

GnomAD4 genome

AF:

0.0290

AC:

4414

AN:

152222

Hom.:

100

Cov.:

AF XY:

0.0295

AC XY:

2196

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.0462

AC:

1916

AN:

41468

American (AMR)

AF:

0.0168

AC:

257

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0251

AC:

AN:

3468

East Asian (EAS)

AF:

0.0396

AC:

205

AN:

5182

South Asian (SAS)

AF:

0.0205

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0459

AC:

488

AN:

10628

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0189

AC:

1286

AN:

68028

Other (OTH)

AF:

0.0317

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

225

450

675

900

1125

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

156

208

260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0263

Hom.:

Bravo

AF:

0.0283

Asia WGS

AF:

0.0330

AC:

115

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

4.0

(source)

DANN

Benign

0.79

PhyloP100

0.59

Mutation Taster

=100/0

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over