chr9-28425517-C-G

Variant names:

• chr9-28425517-C-G
• rs1412239
• NM_001258282.3:c.-228+50423G>C

Variant summary

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

The NM_001258282.3(LINGO2):​c.-228+50423G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 151,836 control chromosomes in the GnomAD database, including 5,619 homozygotes. 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 0.26 (5619 hom., cov: 31)
• Consequence: LINGO2 NM_001258282.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.194

Genes affected

LINGO2 (HGNC:21207): (leucine rich repeat and Ig domain containing 2) Predicted to act upstream of or within positive regulation of synapse assembly. Predicted to be integral component of membrane. Predicted to be active in extracellular matrix and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LINGO2	NM_001258282.3	c.-228+50423G>C		intron_variant	Intron 4 of 6	ENST00000698399.1	NP_001245211.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LINGO2	ENST00000698399.1	c.-228+50423G>C		intron_variant	Intron 4 of 6		NM_001258282.3	ENSP00000513694.1

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39120 AN: 151720 Hom.: 5619 Cov.: 31

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.234

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

GnomAD4 genome AF: 0.258 AC: 39119 AN: 151836 Hom.: 5619 Cov.: 31 AF XY: 0.257 AC XY: 19081 AN XY: 74188

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.225

Gnomad4 ASJ AF: 0.252

Gnomad4 EAS AF: 0.176

Gnomad4 SAS AF: 0.192

Gnomad4 FIN AF: 0.378

Gnomad4 NFE AF: 0.318

Gnomad4 OTH AF: 0.232

Alfa AF: 0.301 Hom.: 921

Bravo AF: 0.244

Asia WGS AF: 0.170 AC: 594 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.0
DANN	Benign	0.67

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: rs1412239; hg19: chr9-28425515;