rs321983

chr7-78673231-A-Gchr7-78673231-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.419-45992T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 151,826 control chromosomes in the GnomAD database, including 17,292 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 0.47 (17292 hom., cov: 31)
• Consequence: MAGI2 NM_012301.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.726

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.639 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAGI2	NM_012301.4	c.419-45992T>C		intron_variant		ENST00000354212.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAGI2	ENST00000354212.9	c.419-45992T>C		intron_variant		1	NM_012301.4	P4

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70750 AN: 151706 Hom.: 17256 Cov.: 31

Gnomad AFR AF: 0.584

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.658

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.437

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

GnomAD4 genome AF: 0.467 AC: 70847 AN: 151826 Hom.: 17292 Cov.: 31 AF XY: 0.470 AC XY: 34869 AN XY: 74182

Gnomad4 AFR AF: 0.584

Gnomad4 AMR AF: 0.449

Gnomad4 ASJ AF: 0.289

Gnomad4 EAS AF: 0.657

Gnomad4 SAS AF: 0.421

Gnomad4 FIN AF: 0.365

Gnomad4 NFE AF: 0.414

Gnomad4 OTH AF: 0.442

Alfa AF: 0.413 Hom.: 19073

Bravo AF: 0.475

Asia WGS AF: 0.550 AC: 1909 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	1.1
Dann	Benign	0.71

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: rs321983; hg19: chr7-78302547;