7-78203399-C-T

Position:

• chr7-78203399-C-T

Variant summary

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

The NM_012301.4(MAGI2):​c.2048-2206G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 152,038 control chromosomes in the GnomAD database, including 5,394 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 0.26 (5394 hom., cov: 33)
• Consequence: MAGI2 NM_012301.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.643

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]

MAGI2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGI2	NM_012301.4	c.2048-2206G>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.2048-2206G>A		intron_variant		1	NM_012301.4	ENSP00000346151.4

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39281 AN: 151920 Hom.: 5393 Cov.: 33

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.280

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

GnomAD4 genome AF: 0.258 AC: 39291 AN: 152038 Hom.: 5394 Cov.: 33 AF XY: 0.261 AC XY: 19411 AN XY: 74314

Gnomad4 AFR AF: 0.181

Gnomad4 AMR AF: 0.317

Gnomad4 ASJ AF: 0.228

Gnomad4 EAS AF: 0.172

Gnomad4 SAS AF: 0.319

Gnomad4 FIN AF: 0.304

Gnomad4 NFE AF: 0.288

Gnomad4 OTH AF: 0.279

Alfa AF: 0.281 Hom.: 8149

Bravo AF: 0.254

Asia WGS AF: 0.242 AC: 843 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	11
DANN	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs10499837; hg19: chr7-77832716;