chr7-78600926-A-G

Position:

• chr7-78600926-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_012301.4(MAGI2):​c.538+26194T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 152,042 control chromosomes in the GnomAD database, including 12,153 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 0.38 (12153 hom., cov: 33)
• Consequence: MAGI2 NM_012301.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.84

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGI2	NM_012301.4	c.538+26194T>C		intron_variant		ENST00000354212.9	NP_036433.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGI2	ENST00000354212.9	c.538+26194T>C		intron_variant		1	NM_012301.4	ENSP00000346151.4

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57446 AN: 151924 Hom.: 12133 Cov.: 33

Gnomad AFR AF: 0.572

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.344

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

GnomAD4 genome AF: 0.378 AC: 57505 AN: 152042 Hom.: 12153 Cov.: 33 AF XY: 0.365 AC XY: 27099 AN XY: 74338

Gnomad4 AFR AF: 0.572

Gnomad4 AMR AF: 0.264

Gnomad4 ASJ AF: 0.255

Gnomad4 EAS AF: 0.135

Gnomad4 SAS AF: 0.171

Gnomad4 FIN AF: 0.266

Gnomad4 NFE AF: 0.343

Gnomad4 OTH AF: 0.341

Alfa AF: 0.341 Hom.: 13394

Bravo AF: 0.391

Asia WGS AF: 0.161 AC: 560 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	15
DANN	Benign	0.95

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: rs319872; hg19: chr7-78230243; COSMIC: COSV62642297;