rs246462

Positions:

• chr7-78813858-A-G
• chr7-78813858-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012301.4(MAGI2):​c.419-186619T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 150,728 control chromosomes in the GnomAD database, including 8,196 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 0.32 (8196 hom., cov: 29)
• Consequence: MAGI2 NM_012301.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.599

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGI2	NM_012301.4	c.419-186619T>C		intron_variant		ENST00000354212.9	NP_036433.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGI2	ENST00000354212.9	c.419-186619T>C		intron_variant		1	NM_012301.4	ENSP00000346151	P4
MAGI2	ENST00000419488.5	c.419-186619T>C		intron_variant		1		ENSP00000405766	A2
MAGI2	ENST00000522391.3	c.419-186619T>C		intron_variant		5		ENSP00000428389	A2
MAGI2	ENST00000637441.1	c.419-186619T>C		intron_variant		5		ENSP00000489633

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47578 AN: 150618 Hom.: 8199 Cov.: 29

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.519

Gnomad SAS AF: 0.327

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.341

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.328

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

GnomAD4 genome AF: 0.316 AC: 47578 AN: 150728 Hom.: 8196 Cov.: 29 AF XY: 0.314 AC XY: 23087 AN XY: 73478

Gnomad4 AFR AF: 0.184

Gnomad4 AMR AF: 0.295

Gnomad4 ASJ AF: 0.367

Gnomad4 EAS AF: 0.520

Gnomad4 SAS AF: 0.325

Gnomad4 FIN AF: 0.336

Gnomad4 NFE AF: 0.378

Gnomad4 OTH AF: 0.329

Alfa AF: 0.345 Hom.: 1509

Bravo AF: 0.314

Asia WGS AF: 0.394 AC: 1368 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.6
DANN	Benign	0.77

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

Publications

LitVar

Other links and lift over

dbSNP: rs246462; hg19: chr7-78443174;