Variant chr7-78019414-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_012301.4(MAGI2):c.4269G>C(p.Pro1423=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 1,128,038 control chromosomes in the GnomAD database, including 30,428 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6856 hom., cov: 29)

Exomes 𝑓: 0.21 ( 23572 hom. )

Consequence

MAGI2
NM_012301.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.15

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 7-78019414-C-G is Benign according to our data. Variant chr7-78019414-C-G is described in ClinVar as [Benign]. Clinvar id is 95513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-78019414-C-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.15 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGI2	NM_012301.4 linkuse as main transcript	c.4269G>C	p.Pro1423=	synonymous_variant	22/22	ENST00000354212.9	NP_036433.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGI2	ENST00000354212.9 linkuse as main transcript	c.4269G>C	p.Pro1423=	synonymous_variant	22/22	1	NM_012301.4	ENSP00000346151	P4	Q86UL8-1

Frequencies

GnomAD3 genomes

AF:

0.283

AC:

41184

AN:

145556

Hom.:

6851

Cov.:

show subpopulations

Gnomad AFR

AF:

0.404

Gnomad AMI

AF:

0.210

Gnomad AMR

AF:

0.309

Gnomad ASJ

AF:

0.273

Gnomad EAS

AF:

0.561

Gnomad SAS

AF:

0.352

Gnomad FIN

AF:

0.243

Gnomad MID

AF:

0.265

Gnomad NFE

AF:

0.184

Gnomad OTH

AF:

0.253

GnomAD3 exomes

AF:

0.349

AC:

259

AN:

742

Hom.:

AF XY:

0.362

AC XY:

178

AN XY:

492

show subpopulations

Gnomad AFR exome

AF:

0.500

Gnomad AMR exome

AF:

0.569

Gnomad ASJ exome

AF:

0.313

Gnomad EAS exome

AF:

0.500

Gnomad SAS exome

AF:

0.508

Gnomad FIN exome

AF:

0.324

Gnomad NFE exome

AF:

0.269

Gnomad OTH exome

AF:

0.458

GnomAD4 exome

AF:

0.205

AC:

201647

AN:

982416

Hom.:

23572

Cov.:

AF XY:

0.205

AC XY:

95060

AN XY:

462686

show subpopulations

Gnomad4 AFR exome

AF:

0.420

Gnomad4 AMR exome

AF:

0.373

Gnomad4 ASJ exome

AF:

0.277

Gnomad4 EAS exome

AF:

0.593

Gnomad4 SAS exome

AF:

0.338

Gnomad4 FIN exome

AF:

0.226

Gnomad4 NFE exome

AF:

0.185

Gnomad4 OTH exome

AF:

0.250

GnomAD4 genome

AF:

0.283

AC:

41214

AN:

145622

Hom.:

6856

Cov.:

AF XY:

0.288

AC XY:

20434

AN XY:

70856

show subpopulations

Gnomad4 AFR

AF:

0.404

Gnomad4 AMR

AF:

0.309

Gnomad4 ASJ

AF:

0.273

Gnomad4 EAS

AF:

0.560

Gnomad4 SAS

AF:

0.353

Gnomad4 FIN

AF:

0.243

Gnomad4 NFE

AF:

0.184

Gnomad4 OTH

AF:

0.255

Alfa

AF:

0.238

Hom.:

619

Bravo

AF:

0.295

Asia WGS

AF:

0.438

AC:

1421

AN:

3254

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 20, 2019	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Oct 22, 2013	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Mar 01, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

5.9

DANN

Benign

0.82

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