7-78114305-T-C

Position:

• chr7-78114305-T-C

Variant summary

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

The NM_012301.4(MAGI2):​c.3567+11389A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 152,074 control chromosomes in the GnomAD database, including 18,792 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 0.50 (18792 hom., cov: 33)
• Consequence: MAGI2 NM_012301.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.193

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGI2	NM_012301.4	c.3567+11389A>G		intron_variant		ENST00000354212.9	NP_036433.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGI2	ENST00000354212.9	c.3567+11389A>G		intron_variant		1	NM_012301.4	ENSP00000346151.4

Frequencies

GnomAD3 genomes AF: 0.495 AC: 75280 AN: 151956 Hom.: 18760 Cov.: 33

Gnomad AFR AF: 0.553

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.449

Gnomad EAS AF: 0.376

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.559

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.487

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

GnomAD4 genome AF: 0.496 AC: 75372 AN: 152074 Hom.: 18792 Cov.: 33 AF XY: 0.494 AC XY: 36737 AN XY: 74348

Gnomad4 AFR AF: 0.553

Gnomad4 AMR AF: 0.445

Gnomad4 ASJ AF: 0.449

Gnomad4 EAS AF: 0.377

Gnomad4 SAS AF: 0.438

Gnomad4 FIN AF: 0.559

Gnomad4 NFE AF: 0.480

Gnomad4 OTH AF: 0.493

Alfa AF: 0.469 Hom.: 14675

Bravo AF: 0.492

Asia WGS AF: 0.434 AC: 1508 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.3
DANN	Benign	0.70

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: rs3807728; hg19: chr7-77743622;