7-78245371-C-T

Position:

• chr7-78245371-C-T

Variant summary

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

The NM_012301.4(MAGI2):​c.2047+10572G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 152,164 control chromosomes in the GnomAD database, including 25,876 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 0.55 (25876 hom., cov: 33)
• Consequence: MAGI2 NM_012301.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.218

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.83 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAGI2	NM_012301.4	c.2047+10572G>A		intron_variant		ENST00000354212.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAGI2	ENST00000354212.9	c.2047+10572G>A		intron_variant		1	NM_012301.4	P4

Frequencies

GnomAD3 genomes AF: 0.547 AC: 83223 AN: 152046 Hom.: 25804 Cov.: 33

Gnomad AFR AF: 0.837

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.546

Gnomad EAS AF: 0.743

Gnomad SAS AF: 0.671

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.510

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

GnomAD4 genome AF: 0.548 AC: 83360 AN: 152164 Hom.: 25876 Cov.: 33 AF XY: 0.551 AC XY: 41009 AN XY: 74366

Gnomad4 AFR AF: 0.838

Gnomad4 AMR AF: 0.435

Gnomad4 ASJ AF: 0.546

Gnomad4 EAS AF: 0.743

Gnomad4 SAS AF: 0.670

Gnomad4 FIN AF: 0.415

Gnomad4 NFE AF: 0.397

Gnomad4 OTH AF: 0.517

Alfa AF: 0.419 Hom.: 22133

Bravo AF: 0.557

Asia WGS AF: 0.727 AC: 2525 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	4.2
DANN	Benign	0.40

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: rs798356; hg19: chr7-77874688;