chr7-78446317-T-C

Variant names:

• chr7-78446317-T-C
• rs10260177
• NM_012301.4:c.1045+43444A>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.1045+43444A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.871 in 151,966 control chromosomes in the GnomAD database, including 57,726 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 0.87 (57726 hom., cov: 31)
• Consequence: MAGI2 NM_012301.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• 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

ENSG00000285892 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.918 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGI2	NM_012301.4	c.1045+43444A>G		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.1045+43444A>G		intron_variant	Intron 6 of 21	1	NM_012301.4	ENSP00000346151.4

Frequencies

GnomAD3 genomes AF: 0.871 AC: 132231 AN: 151848 Hom.: 57700 Cov.: 31

Gnomad AFR AF: 0.806

Gnomad AMI AF: 0.924

Gnomad AMR AF: 0.927

Gnomad ASJ AF: 0.920

Gnomad EAS AF: 0.940

Gnomad SAS AF: 0.864

Gnomad FIN AF: 0.879

Gnomad MID AF: 0.937

Gnomad NFE AF: 0.887

Gnomad OTH AF: 0.887

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

GnomAD4 genome AF: 0.871 AC: 132310 AN: 151966 Hom.: 57726 Cov.: 31 AF XY: 0.873 AC XY: 64825 AN XY: 74284

African (AFR) AF: 0.806 AC: 33424 AN: 41458

American (AMR) AF: 0.927 AC: 14107 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.920 AC: 3192 AN: 3470

East Asian (EAS) AF: 0.940 AC: 4866 AN: 5174

South Asian (SAS) AF: 0.864 AC: 4164 AN: 4822

European-Finnish (FIN) AF: 0.879 AC: 9298 AN: 10572

Middle Eastern (MID) AF: 0.939 AC: 276 AN: 294

European-Non Finnish (NFE) AF: 0.887 AC: 60286 AN: 67948

Other (OTH) AF: 0.883 AC: 1854 AN: 2100

Alfa AF: 0.884 Hom.: 28450

Bravo AF: 0.874

Asia WGS AF: 0.855 AC: 2970 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.2
DANN	Benign	0.43
PhyloP100		0.0
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: rs10260177; hg19: chr7-78075634;