rs12705417

Positions:

• chr7-78389524-G-A

Variant summary

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

The NM_012301.4(MAGI2):​c.1046-20311C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,188 control chromosomes in the GnomAD database, including 2,145 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 0.16 (2145 hom., cov: 33)
• Consequence: MAGI2 NM_012301.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0320

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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGI2	NM_012301.4	c.1046-20311C>T		intron_variant		ENST00000354212.9	NP_036433.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGI2	ENST00000354212.9	c.1046-20311C>T		intron_variant		1	NM_012301.4	ENSP00000346151	P4

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24613 AN: 152070 Hom.: 2146 Cov.: 33

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.0504

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.142

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

GnomAD4 genome AF: 0.162 AC: 24621 AN: 152188 Hom.: 2145 Cov.: 33 AF XY: 0.162 AC XY: 12059 AN XY: 74404

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.102

Gnomad4 ASJ AF: 0.220

Gnomad4 EAS AF: 0.0500

Gnomad4 SAS AF: 0.223

Gnomad4 FIN AF: 0.199

Gnomad4 NFE AF: 0.178

Gnomad4 OTH AF: 0.141

Alfa AF: 0.160 Hom.: 346

Bravo AF: 0.152

Asia WGS AF: 0.134 AC: 467 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.7
DANN	Benign	0.86

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: rs12705417; hg19: chr7-78018841;