chr7-79453347-C-T

Variant names:

• chr7-79453347-C-T
• rs115112916
• NM_012301.4:c.-27G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.11
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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 VariationId is 1316173.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 24 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012301.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGI2	NM_012301.4	MANE Select	c.-27G>A		5_prime_UTR	Exon 1 of 22	NP_036433.2
	MAGI2	NM_001301128.2		c.-27G>A		5_prime_UTR	Exon 1 of 21	NP_001288057.1	Q86UL8-2
	MAGI2-AS3	NR_038345.1		n.235+156C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGI2	ENST00000354212.9	TSL:1 MANE Select	c.-27G>A		5_prime_UTR	Exon 1 of 22	ENSP00000346151.4	Q86UL8-1
	MAGI2	ENST00000419488.5	TSL:1	c.-27G>A		5_prime_UTR	Exon 1 of 21	ENSP00000405766.1	Q86UL8-2
	MAGI2	ENST00000522391.3	TSL:5	c.-27G>A		5_prime_UTR	Exon 1 of 23	ENSP00000428389.1	E7EWI0

Frequencies

GnomAD3 genomes AF: 0.0122 AC: 1855 AN: 152140 Hom.: 24 Cov.: 32

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

GnomAD2 exomes AF: 0.00540 AC: 1203 AN: 222904 AF XY: 0.00519

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 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.: 63 Cov.: 31 AF XY: 0.00260 AC XY: 1837 AN XY: 707496

African (AFR) AF: 0.0445 AC: 1429 AN: 32090

American (AMR) AF: 0.00175 AC: 71 AN: 40568

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24154

East Asian (EAS) AF: 0.00963 AC: 378 AN: 39250

South Asian (SAS) AF: 0.0160 AC: 1303 AN: 81364

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51834

Middle Eastern (MID) AF: 0.00233 AC: 13 AN: 5584

European-Non Finnish (NFE) AF: 0.0000466 AC: 51 AN: 1095496

Other (OTH) AF: 0.00351 AC: 206 AN: 58748

GnomAD4 genome AF: 0.0122 AC: 1857 AN: 152258 Hom.: 24 Cov.: 32 AF XY: 0.0123 AC XY: 912 AN XY: 74436

African (AFR) AF: 0.0394 AC: 1638 AN: 41546

American (AMR) AF: 0.00418 AC: 64 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00853 AC: 44 AN: 5158

South Asian (SAS) AF: 0.0186 AC: 90 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68012

Other (OTH) AF: 0.00520 AC: 11 AN: 2114

Alfa AF: 0.00604 Hom.: 10

Bravo AF: 0.0136

Asia WGS AF: 0.0140 AC: 49 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	16
DANN	Benign	0.83
PhyloP100		1.1
PromoterAI		0.028	Neutral
Mutation Taster		=300/0	polymorphism

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

Other links and lift over

dbSNP: rs115112916; hg19: chr7-79082663;