rs10491633

Positions:

• chr9-28943697-C-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+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 NM_001258282.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.370

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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LINGO2	NM_001258282.3	c.-395+4121G>A		intron_variant		ENST00000698399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LINGO2	ENST00000698399.1	c.-395+4121G>A		intron_variant			NM_001258282.3	P1
LINGO2	ENST00000698401.1	c.-765+4121G>A		intron_variant				P1
LINGO2	ENST00000698402.1	c.-550+4121G>A		intron_variant				P1
LINGO2	ENST00000698404.1	c.-506+4121G>A		intron_variant

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

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.0919

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.121

Gnomad4 SAS AF: 0.156

Gnomad4 FIN AF: 0.106

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.119

Alfa AF: 0.120 Hom.: 183

Bravo AF: 0.116

Asia WGS AF: 0.136 AC: 470 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10491633; hg19: chr9-28943695;