7-78826832-C-T

Position:

• chr7-78826832-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.418+180258G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.605 in 151,836 control chromosomes in the GnomAD database, including 29,248 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 0.61 (29248 hom., cov: 31)
• Consequence: MAGI2 NM_012301.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.73

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=-1.05).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.804 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGI2	NM_012301.4	c.418+180258G>A		intron_variant		ENST00000354212.9	NP_036433.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGI2	ENST00000354212.9	c.418+180258G>A		intron_variant		1	NM_012301.4	ENSP00000346151.4
MAGI2	ENST00000419488.5	c.418+180258G>A		intron_variant		1		ENSP00000405766.1
MAGI2	ENST00000522391.3	c.418+180258G>A		intron_variant		5		ENSP00000428389.1
MAGI2	ENST00000637441.1	c.418+180258G>A		intron_variant		5		ENSP00000489633.1

Frequencies

GnomAD3 genomes AF: 0.605 AC: 91783 AN: 151718 Hom.: 29190 Cov.: 31

Gnomad AFR AF: 0.811

Gnomad AMI AF: 0.581

Gnomad AMR AF: 0.646

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.578

Gnomad FIN AF: 0.552

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.504

Gnomad OTH AF: 0.600

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

GnomAD4 genome AF: 0.605 AC: 91902 AN: 151836 Hom.: 29248 Cov.: 31 AF XY: 0.606 AC XY: 44928 AN XY: 74164

Gnomad4 AFR AF: 0.811

Gnomad4 AMR AF: 0.646

Gnomad4 ASJ AF: 0.523

Gnomad4 EAS AF: 0.359

Gnomad4 SAS AF: 0.579

Gnomad4 FIN AF: 0.552

Gnomad4 NFE AF: 0.504

Gnomad4 OTH AF: 0.599

Alfa AF: 0.523 Hom.: 28961

Bravo AF: 0.618

Asia WGS AF: 0.534 AC: 1856 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.49
DANN	Benign	0.76

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: rs519514; hg19: chr7-78456148;