NM_001258282.3:c.-227-41473T>C

Variant names:

• chr9-28414341-A-G
• rs10968576
• NM_001258282.3:c.-227-41473T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 198 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001258282.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINGO2	NM_001258282.3	MANE Select	c.-227-41473T>C		intron	N/A	NP_001245211.1
	LINGO2	NM_001354574.2		c.-195+61599T>C		intron	N/A	NP_001341503.1
	LINGO2	NM_001354575.2		c.-227-41473T>C		intron	N/A	NP_001341504.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINGO2	ENST00000698399.1	MANE Select	c.-227-41473T>C		intron	N/A	ENSP00000513694.1
	LINGO2	ENST00000379992.6	TSL:5	c.-278-41473T>C		intron	N/A	ENSP00000369328.1
	LINGO2	ENST00000698400.1		c.-442-41473T>C		intron	N/A	ENSP00000513695.1

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

African (AFR) AF: 0.162 AC: 6722 AN: 41486

American (AMR) AF: 0.225 AC: 3421 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 868 AN: 3468

East Asian (EAS) AF: 0.177 AC: 916 AN: 5170

South Asian (SAS) AF: 0.186 AC: 897 AN: 4814

European-Finnish (FIN) AF: 0.376 AC: 3954 AN: 10528

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.316 AC: 21461 AN: 67950

Other (OTH) AF: 0.230 AC: 484 AN: 2106

Alfa AF: 0.287 Hom.: 27086

Bravo AF: 0.243

Asia WGS AF: 0.169 AC: 587 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.012
DANN	Benign	0.34
PhyloP100		-5.8
Mutation Taster		=100/0	polymorphism (auto)

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: rs10968576; hg19: chr9-28414339;