rs10968576

chr9-28414341-A-G

Variant summary

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

The NM_001258282.3(LINGO2):c.-227-41473T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 151,932 control chromosomes in the GnomAD database, including 5,556 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 (5556 hom., cov: 31)
• Consequence: LINGO2 NM_001258282.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.83

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=-1.04).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LINGO2	NM_001258282.3	c.-227-41473T>C		intron_variant		ENST00000698399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LINGO2	ENST00000698399.1	c.-227-41473T>C		intron_variant			NM_001258282.3	P1

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38904 AN: 151814 Hom.: 5556 Cov.: 31

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.232

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

GnomAD4 genome AF: 0.256 AC: 38904 AN: 151932 Hom.: 5556 Cov.: 31 AF XY: 0.255 AC XY: 18962 AN XY: 74246

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.225

Gnomad4 ASJ AF: 0.250

Gnomad4 EAS AF: 0.177

Gnomad4 SAS AF: 0.186

Gnomad4 FIN AF: 0.376

Gnomad4 NFE AF: 0.316

Gnomad4 OTH AF: 0.230

Alfa AF: 0.292 Hom.: 14385

Bravo AF: 0.243

Asia WGS AF: 0.169 AC: 587 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.012
Dann	Benign	0.34

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: rs10968576; hg19: chr9-28414339;