rs10491633

Variant names:

• chr9-28943697-C-T
• rs10491633
• NM_001258282.3:c.-395+4121G>A

Variant summary

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

The ENST00000698399.1(LINGO2):​c.-395+4121G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,036 control chromosomes in the GnomAD database, including 1,071 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 0.12 (1071 hom., cov: 32)
• Consequence: LINGO2 ENST00000698399.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.370
• Publications: 2 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000698399.1. 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.-395+4121G>A		intron	N/A	NP_001245211.1
	LINGO2	NM_001354574.2		c.-362+4121G>A		intron	N/A	NP_001341503.1
	LINGO2	NM_001354575.2		c.-395+4121G>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.-395+4121G>A		intron	N/A	ENSP00000513694.1
	LINGO2	ENST00000698401.1		c.-765+4121G>A		intron	N/A	ENSP00000513696.1
	LINGO2	ENST00000698402.1		c.-550+4121G>A		intron	N/A	ENSP00000513697.1

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18068 AN: 151918 Hom.: 1073 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.0614

Gnomad AMR AF: 0.0920

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.120

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

GnomAD4 genome AF: 0.119 AC: 18084 AN: 152036 Hom.: 1071 Cov.: 32 AF XY: 0.120 AC XY: 8901 AN XY: 74304

African (AFR) AF: 0.135 AC: 5589 AN: 41458

American (AMR) AF: 0.0919 AC: 1404 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 437 AN: 3468

East Asian (EAS) AF: 0.121 AC: 624 AN: 5172

South Asian (SAS) AF: 0.156 AC: 749 AN: 4816

European-Finnish (FIN) AF: 0.106 AC: 1121 AN: 10560

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.115 AC: 7812 AN: 67966

Other (OTH) AF: 0.119 AC: 251 AN: 2112

Alfa AF: 0.120 Hom.: 187

Bravo AF: 0.116

Asia WGS AF: 0.136 AC: 470 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.2
DANN	Benign	0.56
PhyloP100		-0.37

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10491633; hg19: chr9-28943695;