rs1990577

chr7-78489882-A-Cchr7-78489882-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_012301.4(MAGI2):c.966-42T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 1,432,782 control chromosomes in the GnomAD database, including 223,275 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.57 (24049 hom., cov: 30)
  • Exomes 𝑓: 0.55 (199226 hom.)
• Consequence: MAGI2 NM_012301.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.03

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=-0.38).
• BP6: Variant 7-78489882-A-C is Benign according to our data. Variant chr7-78489882-A-C is described in ClinVar as [Benign]. Clinvar id is 1237001.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAGI2	NM_012301.4	c.966-42T>G		intron_variant		ENST00000354212.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAGI2	ENST00000354212.9	c.966-42T>G		intron_variant		1	NM_012301.4	P4

Frequencies

GnomAD3 genomes AF: 0.571 AC: 84585 AN: 148040 Hom.: 24030 Cov.: 30

Gnomad AFR AF: 0.548

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.655

Gnomad ASJ AF: 0.536

Gnomad EAS AF: 0.774

Gnomad SAS AF: 0.668

Gnomad FIN AF: 0.594

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.576

GnomAD3 exomes AF: 0.606 AC: 133969 AN: 221162 Hom.: 40893 AF XY: 0.601 AC XY: 72085 AN XY: 120026

Gnomad AFR exome AF: 0.539

Gnomad AMR exome AF: 0.751

Gnomad ASJ exome AF: 0.565

Gnomad EAS exome AF: 0.774

Gnomad SAS exome AF: 0.662

Gnomad FIN exome AF: 0.582

Gnomad NFE exome AF: 0.546

Gnomad OTH exome AF: 0.584

GnomAD4 exome AF: 0.553 AC: 710326 AN: 1284628 Hom.: 199226 Cov.: 17 AF XY: 0.554 AC XY: 358118 AN XY: 646316

Gnomad4 AFR exome AF: 0.526

Gnomad4 AMR exome AF: 0.725

Gnomad4 ASJ exome AF: 0.546

Gnomad4 EAS exome AF: 0.761

Gnomad4 SAS exome AF: 0.647

Gnomad4 FIN exome AF: 0.576

Gnomad4 NFE exome AF: 0.531

Gnomad4 OTH exome AF: 0.554

GnomAD4 genome AF: 0.571 AC: 84643 AN: 148154 Hom.: 24049 Cov.: 30 AF XY: 0.577 AC XY: 41681 AN XY: 72180

Gnomad4 AFR AF: 0.548

Gnomad4 AMR AF: 0.655

Gnomad4 ASJ AF: 0.536

Gnomad4 EAS AF: 0.775

Gnomad4 SAS AF: 0.668

Gnomad4 FIN AF: 0.594

Gnomad4 NFE AF: 0.544

Gnomad4 OTH AF: 0.572

Alfa AF: 0.531 Hom.: 11951

Bravo AF: 0.561

Asia WGS AF: 0.682 AC: 2371 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 20, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
Cadd	Benign	18
Dann	Benign	0.85

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: rs1990577; hg19: chr7-78119199;