rs113527903

Positions:

• chr7-78209193-C-G
• chr7-78209193-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012301.4(MAGI2):​c.2048-8000G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.090 (274 hom., cov: 4)
• Consequence: MAGI2 NM_012301.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.838

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]

LOC124901684 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGI2	NM_012301.4	c.2048-8000G>C		intron_variant		ENST00000354212.9	NP_036433.2
LOC124901684	XR_007060400.1	n.422-3160C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGI2	ENST00000354212.9	c.2048-8000G>C		intron_variant		1	NM_012301.4	ENSP00000346151	P4

Frequencies

GnomAD3 genomes AF: 0.0897 AC: 2654 AN: 29600 Hom.: 274 Cov.: 4

Gnomad AFR AF: 0.0374

Gnomad AMI AF: 0.0547

Gnomad AMR AF: 0.0664

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.0528

Gnomad SAS AF: 0.0482

Gnomad FIN AF: 0.0281

Gnomad MID AF: 0.0625

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.112

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0896 AC: 2654 AN: 29630 Hom.: 274 Cov.: 4 AF XY: 0.0843 AC XY: 1169 AN XY: 13872

Gnomad4 AFR AF: 0.0373

Gnomad4 AMR AF: 0.0663

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.0529

Gnomad4 SAS AF: 0.0485

Gnomad4 FIN AF: 0.0281

Gnomad4 NFE AF: 0.153

Gnomad4 OTH AF: 0.111

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.1
DANN	Benign	0.72

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: rs113527903; hg19: chr7-77838510;