7-78462650-G-C

Position:

• chr7-78462650-G-C

Variant summary

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

The NM_012301.4(MAGI2):​c.1045+27111C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 151,992 control chromosomes in the GnomAD database, including 24,020 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 (24020 hom., cov: 32)
• Consequence: MAGI2 NM_012301.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.495

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.644 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAGI2	NM_012301.4	c.1045+27111C>G		intron_variant		ENST00000354212.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAGI2	ENST00000354212.9	c.1045+27111C>G		intron_variant		1	NM_012301.4	P4

Frequencies

GnomAD3 genomes AF: 0.545 AC: 82840 AN: 151874 Hom.: 24002 Cov.: 32

Gnomad AFR AF: 0.335

Gnomad AMI AF: 0.682

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.696

Gnomad EAS AF: 0.663

Gnomad SAS AF: 0.644

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.640

Gnomad OTH AF: 0.599

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

GnomAD4 genome AF: 0.545 AC: 82906 AN: 151992 Hom.: 24020 Cov.: 32 AF XY: 0.546 AC XY: 40540 AN XY: 74250

Gnomad4 AFR AF: 0.336

Gnomad4 AMR AF: 0.535

Gnomad4 ASJ AF: 0.696

Gnomad4 EAS AF: 0.662

Gnomad4 SAS AF: 0.645

Gnomad4 FIN AF: 0.596

Gnomad4 NFE AF: 0.640

Gnomad4 OTH AF: 0.599

Alfa AF: 0.453 Hom.: 1339

Bravo AF: 0.531

Asia WGS AF: 0.608 AC: 2112 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.95
DANN	Benign	0.30

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: rs2160322; hg19: chr7-78091967;