rs10491629

chr9-28855157-G-T

Variant summary

Our verdict is Benign. Variant got -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

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=-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/exons	MANE	UniProt
LINGO2	NM_001258282.3	c.-395+92661C>A		intron_variant		ENST00000698399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LINGO2	ENST00000698399.1	c.-395+92661C>A		intron_variant			NM_001258282.3	P1
LINGO2	ENST00000698401.1	c.-765+92661C>A		intron_variant				P1
LINGO2	ENST00000698402.1	c.-550+92661C>A		intron_variant				P1
LINGO2	ENST00000698404.1	c.-506+92661C>A		intron_variant

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

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.0812

Gnomad4 ASJ AF: 0.0609

Gnomad4 EAS AF: 0.107

Gnomad4 SAS AF: 0.0927

Gnomad4 FIN AF: 0.0980

Gnomad4 NFE AF: 0.0758

Gnomad4 OTH AF: 0.0838

Alfa AF: 0.0967 Hom.: 178

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10491629; hg19: chr9-28855155;