7-78720085-A-T

Variant names:

• chr7-78720085-A-T
• rs10485915
• NM_012301.4:c.419-92846T>A

Variant summary

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

The NM_012301.4(MAGI2):​c.419-92846T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0523 in 152,192 control chromosomes in the GnomAD database, including 365 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 0.052 (365 hom., cov: 32)
• Consequence: MAGI2 NM_012301.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.356

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGI2	NM_012301.4	c.419-92846T>A		intron_variant	Intron 2 of 21	ENST00000354212.9	NP_036433.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGI2	ENST00000354212.9	c.419-92846T>A		intron_variant	Intron 2 of 21	1	NM_012301.4	ENSP00000346151.4

Frequencies

GnomAD3 genomes AF: 0.0522 AC: 7933 AN: 152074 Hom.: 362 Cov.: 32

Gnomad AFR AF: 0.0866

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0263

Gnomad ASJ AF: 0.0320

Gnomad EAS AF: 0.202

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.0758

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0198

Gnomad OTH AF: 0.0507

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

GnomAD4 genome AF: 0.0523 AC: 7964 AN: 152192 Hom.: 365 Cov.: 32 AF XY: 0.0573 AC XY: 4263 AN XY: 74418

Gnomad4 AFR AF: 0.0872

Gnomad4 AMR AF: 0.0262

Gnomad4 ASJ AF: 0.0320

Gnomad4 EAS AF: 0.202

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.0758

Gnomad4 NFE AF: 0.0198

Gnomad4 OTH AF: 0.0501

Alfa AF: 0.0119 Hom.: 4

Bravo AF: 0.0493

Asia WGS AF: 0.144 AC: 498 AN: 3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.0
DANN	Benign	0.50

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: rs10485915; hg19: chr7-78349401;