Genetic Variant MAGI2:c.-27G>A (chr7-79453347-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_012301.4(MAGI2):c.-27G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00336 in 1,581,346 control chromosomes in the GnomAD database, including 87 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 24 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 63 hom. )

Consequence

MAGI2
NM_012301.4 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.11

Variant links:

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 links:

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

MAGI2-AS3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 7-79453347-C-T is Benign according to our data. Variant chr7-79453347-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1316173.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-79453347-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0122 (1857/152258) while in subpopulation AFR AF= 0.0394 (1638/41546). AF 95% confidence interval is 0.0378. There are 24 homozygotes in gnomad4. There are 912 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 24 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGI2	NM_012301.4 link	c.-27G>A		5_prime_UTR_variant	Exon 1 of 22	ENST00000354212.9	NP_036433.2	Q86UL8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGI2	ENST00000354212.9 link	c.-27G>A		5_prime_UTR_variant	Exon 1 of 22	1	NM_012301.4	ENSP00000346151.4		Q86UL8-1

Frequencies

GnomAD3 genomes

AF:

0.0122

AC:

1855

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0395

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00419

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00851

Gnomad SAS

AF:

0.0188

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00540

AC:

1203

AN:

222904

Hom.:

AF XY:

0.00519

AC XY:

626

AN XY:

120600

show subpopulations

Gnomad AFR exome

AF:

0.0431

Gnomad AMR exome

AF:

0.00132

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00430

Gnomad SAS exome

AF:

0.0181

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000486

Gnomad OTH exome

AF:

0.00232

GnomAD4 exome

AF:

0.00241

AC:

3451

AN:

1429088

Hom.:

Cov.:

AF XY:

0.00260

AC XY:

1837

AN XY:

707496

show subpopulations

Gnomad4 AFR exome

AF:

0.0445

Gnomad4 AMR exome

AF:

0.00175

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00963

Gnomad4 SAS exome

AF:

0.0160

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000466

Gnomad4 OTH exome

AF:

0.00351

GnomAD4 genome

AF:

0.0122

AC:

1857

AN:

152258

Hom.:

Cov.:

AF XY:

0.0123

AC XY:

912

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0394

Gnomad4 AMR

AF:

0.00418

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00853

Gnomad4 SAS

AF:

0.0186

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00654

Hom.:

Bravo

AF:

0.0136

Asia WGS

AF:

0.0140

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 04, 2021

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.83

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over