7-79452940-T-A

Position:

• chr7-79452940-T-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000354212.9(MAGI2):​c.301+80A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00414 in 1,440,296 control chromosomes in the GnomAD database, including 209 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.021 (126 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (83 hom.)
• Consequence: MAGI2 ENST00000354212.9 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.100

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-AS3 (HGNC:40862): (MAGI2 antisense RNA 3)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 7-79452940-T-A is Benign according to our data. Variant chr7-79452940-T-A is described in ClinVar as [Benign]. Clinvar id is 1242562.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0707 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGI2	NM_012301.4	c.301+80A>T		intron_variant		ENST00000354212.9	NP_036433.2
MAGI2-AS3	NR_038346.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGI2	ENST00000354212.9	c.301+80A>T		intron_variant		1	NM_012301.4	ENSP00000346151	P4

Frequencies

GnomAD3 genomes AF: 0.0211 AC: 3207 AN: 151896 Hom.: 126 Cov.: 32

Gnomad AFR AF: 0.0731

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00859

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000623

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.0143

GnomAD4 exome AF: 0.00214 AC: 2757 AN: 1288284 Hom.: 83 Cov.: 20 AF XY: 0.00195 AC XY: 1234 AN XY: 633142

Gnomad4 AFR exome AF: 0.0780

Gnomad4 AMR exome AF: 0.00436

Gnomad4 ASJ exome AF: 0.000207

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000161

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000819

Gnomad4 OTH exome AF: 0.00495

GnomAD4 genome AF: 0.0211 AC: 3209 AN: 152012 Hom.: 126 Cov.: 32 AF XY: 0.0205 AC XY: 1523 AN XY: 74330

Gnomad4 AFR AF: 0.0729

Gnomad4 AMR AF: 0.00857

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000624

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000294

Gnomad4 OTH AF: 0.0142

Alfa AF: 0.00334 Hom.: 0

Bravo AF: 0.0237

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 24, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.7
DANN	Benign	0.61

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: rs114233436; hg19: chr7-79082256;