chr7-78140573-T-C

Variant names:

• chr7-78140573-T-C
• rs12668675
• NM_012301.4:c.2846-5367A>G

Variant summary

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

The NM_012301.4(MAGI2):​c.2846-5367A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 152,150 control chromosomes in the GnomAD database, including 11,914 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 0.39 (11914 hom., cov: 33)
• Consequence: MAGI2 NM_012301.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.108
• Publications: 1 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=-0.63).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.411 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.2846-5367A>G		intron	N/A	NP_036433.2
	MAGI2	NM_001301128.2		c.2804-5367A>G		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.2846-5367A>G		intron	N/A	ENSP00000346151.4
	MAGI2	ENST00000419488.5	TSL:1	c.2804-5367A>G		intron	N/A	ENSP00000405766.1
	MAGI2	ENST00000519748.5	TSL:1	c.1625-5367A>G		intron	N/A	ENSP00000486774.1

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59738 AN: 152032 Hom.: 11914 Cov.: 33

Gnomad AFR AF: 0.417

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.392

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

GnomAD4 genome AF: 0.393 AC: 59767 AN: 152150 Hom.: 11914 Cov.: 33 AF XY: 0.385 AC XY: 28646 AN XY: 74400

African (AFR) AF: 0.416 AC: 17274 AN: 41478

American (AMR) AF: 0.409 AC: 6250 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.340 AC: 1181 AN: 3472

East Asian (EAS) AF: 0.269 AC: 1393 AN: 5176

South Asian (SAS) AF: 0.297 AC: 1434 AN: 4828

European-Finnish (FIN) AF: 0.312 AC: 3300 AN: 10592

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.407 AC: 27710 AN: 68004

Other (OTH) AF: 0.395 AC: 834 AN: 2110

Alfa AF: 0.338 Hom.: 2465

Bravo AF: 0.402

Asia WGS AF: 0.306 AC: 1069 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	14
DANN	Benign	0.64
PhyloP100		0.11
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: rs12668675; hg19: chr7-77769890;