7-78489882-A-T

Variant names:

• chr7-78489882-A-T
• rs1990577
• NM_012301.4:c.966-42T>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_012301.4(MAGI2):​c.966-42T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000536 in 1,435,946 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000094 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000049 (0 hom.)
• Consequence: MAGI2 NM_012301.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.03

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGI2	NM_012301.4	c.966-42T>A		intron_variant	Intron 5 of 21	ENST00000354212.9	NP_036433.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGI2	ENST00000354212.9	c.966-42T>A		intron_variant	Intron 5 of 21	1	NM_012301.4	ENSP00000346151.4

Frequencies

GnomAD3 genomes AF: 0.0000945 AC: 14 AN: 148174 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000176

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000677

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000213

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000747

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000588 AC: 13 AN: 221162 Hom.: 0 AF XY: 0.0000250 AC XY: 3 AN XY: 120026

Gnomad AFR exome AF: 0.000396

Gnomad AMR exome AF: 0.0000745

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000387

Gnomad OTH exome AF: 0.000196

GnomAD4 exome AF: 0.0000489 AC: 63 AN: 1287658 Hom.: 0 Cov.: 17 AF XY: 0.0000479 AC XY: 31 AN XY: 647800

Gnomad4 AFR exome AF: 0.000282

Gnomad4 AMR exome AF: 0.0000545

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000129

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000402

Gnomad4 OTH exome AF: 0.000166

GnomAD4 genome AF: 0.0000944 AC: 14 AN: 148288 Hom.: 0 Cov.: 30 AF XY: 0.0000969 AC XY: 7 AN XY: 72272

Gnomad4 AFR AF: 0.000175

Gnomad4 AMR AF: 0.0000676

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000213

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000747

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	17
DANN	Benign	0.87

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: rs1990577; hg19: chr7-78119199;