rs10485909

Variant names:

• chr7-78610431-G-A
• rs10485909
• NM_012301.4:c.538+16689C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-78610431-G-A
• chr7-78610431-G-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.538+16689C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0458 in 152,196 control chromosomes in the GnomAD database, including 227 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 0.046 (227 hom., cov: 32)
• Consequence: MAGI2 NM_012301.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0540
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0727 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGI2	NM_012301.4	c.538+16689C>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.538+16689C>T		intron_variant	Intron 3 of 21	1	NM_012301.4	ENSP00000346151.4

Frequencies

GnomAD3 genomes AF: 0.0458 AC: 6972 AN: 152078 Hom.: 225 Cov.: 32

Gnomad AFR AF: 0.0129

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.0585

Gnomad ASJ AF: 0.0389

Gnomad EAS AF: 0.0790

Gnomad SAS AF: 0.0104

Gnomad FIN AF: 0.0491

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0621

Gnomad OTH AF: 0.0464

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

GnomAD4 genome AF: 0.0458 AC: 6975 AN: 152196 Hom.: 227 Cov.: 32 AF XY: 0.0444 AC XY: 3305 AN XY: 74418

African (AFR) AF: 0.0129 AC: 536 AN: 41536

American (AMR) AF: 0.0584 AC: 893 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0389 AC: 135 AN: 3468

East Asian (EAS) AF: 0.0790 AC: 407 AN: 5152

South Asian (SAS) AF: 0.0102 AC: 49 AN: 4820

European-Finnish (FIN) AF: 0.0491 AC: 520 AN: 10598

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0621 AC: 4222 AN: 68016

Other (OTH) AF: 0.0478 AC: 101 AN: 2112

Alfa AF: 0.0568 Hom.: 462

Bravo AF: 0.0461

Asia WGS AF: 0.0380 AC: 134 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.32
DANN	Benign	0.46
PhyloP100		0.054
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: rs10485909; hg19: chr7-78239748;