9-28181087-C-T

Variant names:

• chr9-28181087-C-T
• rs1319535
• NM_001258282.3:c.-36+114121G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001258282.3(LINGO2):​c.-36+114121G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.623 in 151,814 control chromosomes in the GnomAD database, including 29,667 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 0.62 (29667 hom., cov: 31)
• Consequence: LINGO2 NM_001258282.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0900
• Publications: 5 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.657 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.-36+114121G>A		intron	N/A	NP_001245211.1
	LINGO2	NM_001354574.2		c.-36+114121G>A		intron	N/A	NP_001341503.1
	LINGO2	NM_001354575.2		c.-36+114121G>A		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.-36+114121G>A		intron	N/A	ENSP00000513694.1
	LINGO2	ENST00000379992.6	TSL:5	c.-87+114121G>A		intron	N/A	ENSP00000369328.1
	LINGO2	ENST00000698400.1		c.-250-100109G>A		intron	N/A	ENSP00000513695.1

Frequencies

GnomAD3 genomes AF: 0.623 AC: 94495 AN: 151696 Hom.: 29649 Cov.: 31

Gnomad AFR AF: 0.615

Gnomad AMI AF: 0.669

Gnomad AMR AF: 0.668

Gnomad ASJ AF: 0.604

Gnomad EAS AF: 0.515

Gnomad SAS AF: 0.385

Gnomad FIN AF: 0.604

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.646

Gnomad OTH AF: 0.627

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

GnomAD4 genome AF: 0.623 AC: 94567 AN: 151814 Hom.: 29667 Cov.: 31 AF XY: 0.615 AC XY: 45640 AN XY: 74178

African (AFR) AF: 0.615 AC: 25455 AN: 41386

American (AMR) AF: 0.668 AC: 10174 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.604 AC: 2096 AN: 3468

East Asian (EAS) AF: 0.514 AC: 2637 AN: 5130

South Asian (SAS) AF: 0.384 AC: 1849 AN: 4812

European-Finnish (FIN) AF: 0.604 AC: 6368 AN: 10544

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.646 AC: 43870 AN: 67928

Other (OTH) AF: 0.628 AC: 1326 AN: 2112

Alfa AF: 0.634 Hom.: 59264

Bravo AF: 0.634

Asia WGS AF: 0.484 AC: 1681 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.7
DANN	Benign	0.43
PhyloP100		0.090
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: rs1319535; hg19: chr9-28181085; COSMIC: COSV66143344;