7-78379848-C-T

Position:

• chr7-78379848-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.1046-10635G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.817 in 151,940 control chromosomes in the GnomAD database, including 50,818 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 0.82 (50818 hom., cov: 32)
• Consequence: MAGI2 NM_012301.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.196

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 (AMR) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAGI2	NM_012301.4	c.1046-10635G>A		intron_variant		ENST00000354212.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAGI2	ENST00000354212.9	c.1046-10635G>A		intron_variant		1	NM_012301.4	P4

Frequencies

GnomAD3 genomes AF: 0.817 AC: 124051 AN: 151822 Hom.: 50778 Cov.: 32

Gnomad AFR AF: 0.842

Gnomad AMI AF: 0.844

Gnomad AMR AF: 0.852

Gnomad ASJ AF: 0.851

Gnomad EAS AF: 0.813

Gnomad SAS AF: 0.786

Gnomad FIN AF: 0.805

Gnomad MID AF: 0.796

Gnomad NFE AF: 0.797

Gnomad OTH AF: 0.805

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

GnomAD4 genome AF: 0.817 AC: 124143 AN: 151940 Hom.: 50818 Cov.: 32 AF XY: 0.819 AC XY: 60792 AN XY: 74258

Gnomad4 AFR AF: 0.841

Gnomad4 AMR AF: 0.852

Gnomad4 ASJ AF: 0.851

Gnomad4 EAS AF: 0.812

Gnomad4 SAS AF: 0.787

Gnomad4 FIN AF: 0.805

Gnomad4 NFE AF: 0.797

Gnomad4 OTH AF: 0.804

Alfa AF: 0.810 Hom.: 6198

Bravo AF: 0.821

Asia WGS AF: 0.753 AC: 2612 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.4
DANN	Benign	0.62

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: rs1029819; hg19: chr7-78009165;