7-79453421-A-C

Position:

• chr7-79453421-A-C

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.-101T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00304 in 1,504,246 control chromosomes in the GnomAD database, including 116 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (74 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (42 hom.)
• Consequence: MAGI2 ENST00000354212.9 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0300

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=-0.84).
• BP6: Variant 7-79453421-A-C is Benign according to our data. Variant chr7-79453421-A-C is described in ClinVar as [Benign]. Clinvar id is 1273517.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGI2	NM_012301.4	c.-101T>G		5_prime_UTR_variant	1/22	ENST00000354212.9	NP_036433.2
MAGI2-AS3	NR_038346.1	n.236-166A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGI2	ENST00000354212.9	c.-101T>G		5_prime_UTR_variant	1/22	1	NM_012301.4	ENSP00000346151	P4
MAGI2-AS3	ENST00000426835.6	n.189+230A>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0163 AC: 2484 AN: 152150 Hom.: 75 Cov.: 32

Gnomad AFR AF: 0.0563

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00753

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.0110

GnomAD4 exome AF: 0.00154 AC: 2078 AN: 1351978 Hom.: 42 Cov.: 31 AF XY: 0.00136 AC XY: 902 AN XY: 662232

Gnomad4 AFR exome AF: 0.0548

Gnomad4 AMR exome AF: 0.00442

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000876

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000742

Gnomad4 OTH exome AF: 0.00366

GnomAD4 genome AF: 0.0164 AC: 2490 AN: 152268 Hom.: 74 Cov.: 32 AF XY: 0.0155 AC XY: 1156 AN XY: 74454

Gnomad4 AFR AF: 0.0563

Gnomad4 AMR AF: 0.00752

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.00777 Hom.: 6

Bravo AF: 0.0185

Asia WGS AF: 0.00260 AC: 9 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	Sep 26, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.3
DANN	Benign	0.68

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: rs10279502; hg19: chr7-79082737;