7-78379848-C-T

Variant names:

• chr7-78379848-C-T
• rs1029819
• NM_012301.4:c.1046-10635G>A

Variant summary

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

The NM_012301.4(MAGI2):​c.1046-10635G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.817 in 151,940 control chromosomes in the GnomAD database, including 50,818 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 0.82 (50818 hom., cov: 32)
• Consequence: MAGI2 NM_012301.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.196
• Publications: 3 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGI2	NM_012301.4	c.1046-10635G>A		intron_variant	Intron 6 of 21	ENST00000354212.9	NP_036433.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGI2	ENST00000354212.9	c.1046-10635G>A		intron_variant	Intron 6 of 21	1	NM_012301.4	ENSP00000346151.4

Frequencies

GnomAD3 genomes AF: 0.817 AC: 124051 AN: 151822 Hom.: 50778 Cov.: 32

Gnomad AFR AF: 0.842

Gnomad AMI AF: 0.844

Gnomad AMR AF: 0.852

Gnomad ASJ AF: 0.851

Gnomad EAS AF: 0.813

Gnomad SAS AF: 0.786

Gnomad FIN AF: 0.805

Gnomad MID AF: 0.796

Gnomad NFE AF: 0.797

Gnomad OTH AF: 0.805

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

GnomAD4 genome AF: 0.817 AC: 124143 AN: 151940 Hom.: 50818 Cov.: 32 AF XY: 0.819 AC XY: 60792 AN XY: 74258

African (AFR) AF: 0.841 AC: 34905 AN: 41482

American (AMR) AF: 0.852 AC: 12993 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.851 AC: 2953 AN: 3470

East Asian (EAS) AF: 0.812 AC: 4194 AN: 5162

South Asian (SAS) AF: 0.787 AC: 3791 AN: 4818

European-Finnish (FIN) AF: 0.805 AC: 8487 AN: 10546

Middle Eastern (MID) AF: 0.791 AC: 231 AN: 292

European-Non Finnish (NFE) AF: 0.797 AC: 54122 AN: 67902

Other (OTH) AF: 0.804 AC: 1697 AN: 2112

Alfa AF: 0.812 Hom.: 6480

Bravo AF: 0.821

Asia WGS AF: 0.753 AC: 2612 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.4
DANN	Benign	0.62
PhyloP100		-0.20
Mutation Taster		=15/85	disease causing

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: rs1029819; hg19: chr7-78009165;