NM_001258282.3:c.-395+92661C>A

Variant names:

• chr9-28855157-G-T
• rs10491629
• NM_001258282.3:c.-395+92661C>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.-395+92661C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0949 in 151,862 control chromosomes in the GnomAD database, including 772 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 0.095 (772 hom., cov: 33)
• Consequence: LINGO2 NM_001258282.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.703
• 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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LINGO2	NM_001258282.3	c.-395+92661C>A		intron_variant	Intron 2 of 6	ENST00000698399.1	NP_001245211.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LINGO2	ENST00000698399.1	c.-395+92661C>A		intron_variant	Intron 2 of 6		NM_001258282.3	ENSP00000513694.1
LINGO2	ENST00000698401.1	c.-765+92661C>A		intron_variant	Intron 2 of 7			ENSP00000513696.1
LINGO2	ENST00000698402.1	c.-550+92661C>A		intron_variant	Intron 2 of 7			ENSP00000513697.1
LINGO2	ENST00000698404.1	c.-506+92661C>A		intron_variant	Intron 2 of 8			ENSP00000513699.1

Frequencies

GnomAD3 genomes AF: 0.0949 AC: 14394 AN: 151744 Hom.: 771 Cov.: 33

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0811

Gnomad ASJ AF: 0.0609

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.0928

Gnomad FIN AF: 0.0980

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0758

Gnomad OTH AF: 0.0847

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

GnomAD4 genome AF: 0.0949 AC: 14411 AN: 151862 Hom.: 772 Cov.: 33 AF XY: 0.0957 AC XY: 7101 AN XY: 74234

African (AFR) AF: 0.134 AC: 5558 AN: 41428

American (AMR) AF: 0.0812 AC: 1236 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.0609 AC: 211 AN: 3466

East Asian (EAS) AF: 0.107 AC: 552 AN: 5146

South Asian (SAS) AF: 0.0927 AC: 446 AN: 4812

European-Finnish (FIN) AF: 0.0980 AC: 1035 AN: 10566

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0758 AC: 5149 AN: 67912

Other (OTH) AF: 0.0838 AC: 177 AN: 2112

Alfa AF: 0.0977 Hom.: 191

Bravo AF: 0.0935

Asia WGS AF: 0.0960 AC: 331 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	8.9
DANN	Benign	0.40
PhyloP100		0.70

Splicing

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

Other links and lift over

dbSNP: rs10491629; hg19: chr9-28855155;