chr7-78737259-A-G

Variant names:

• chr7-78737259-A-G
• rs10808167
• NM_012301.4:c.419-110020T>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.419-110020T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 152,014 control chromosomes in the GnomAD database, including 18,558 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 0.49 (18558 hom., cov: 33)
• Consequence: MAGI2 NM_012301.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.96
• Publications: 4 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.534 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.419-110020T>C		intron	N/A	NP_036433.2
	MAGI2	NM_001301128.2		c.419-110020T>C		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.419-110020T>C		intron	N/A	ENSP00000346151.4
	MAGI2	ENST00000419488.5	TSL:1	c.419-110020T>C		intron	N/A	ENSP00000405766.1
	MAGI2	ENST00000522391.3	TSL:5	c.419-110020T>C		intron	N/A	ENSP00000428389.1

Frequencies

GnomAD3 genomes AF: 0.488 AC: 74129 AN: 151898 Hom.: 18553 Cov.: 33

Gnomad AFR AF: 0.478

Gnomad AMI AF: 0.350

Gnomad AMR AF: 0.439

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.506

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

GnomAD4 genome AF: 0.488 AC: 74161 AN: 152014 Hom.: 18558 Cov.: 33 AF XY: 0.478 AC XY: 35536 AN XY: 74312

African (AFR) AF: 0.477 AC: 19780 AN: 41440

American (AMR) AF: 0.439 AC: 6701 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.476 AC: 1653 AN: 3470

East Asian (EAS) AF: 0.303 AC: 1565 AN: 5168

South Asian (SAS) AF: 0.308 AC: 1486 AN: 4818

European-Finnish (FIN) AF: 0.458 AC: 4845 AN: 10570

Middle Eastern (MID) AF: 0.435 AC: 127 AN: 292

European-Non Finnish (NFE) AF: 0.539 AC: 36622 AN: 67966

Other (OTH) AF: 0.503 AC: 1063 AN: 2114

Alfa AF: 0.521 Hom.: 65563

Bravo AF: 0.492

Asia WGS AF: 0.306 AC: 1065 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	11
DANN	Benign	0.52
PhyloP100		3.0
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: rs10808167; hg19: chr7-78366575;