rs10968280

Variant names:

• chr9-28011647-T-A
• rs10968280
• NM_001258282.3:c.-35-60941A>T

Variant summary

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

The NM_001258282.3(LINGO2):​c.-35-60941A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.098 in 152,196 control chromosomes in the GnomAD database, including 731 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 0.098 (731 hom., cov: 32)
• Consequence: LINGO2 NM_001258282.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.116
• Publications: 4 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LINGO2	NM_001258282.3	c.-35-60941A>T		intron_variant	Intron 6 of 6	ENST00000698399.1	NP_001245211.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LINGO2	ENST00000698399.1	c.-35-60941A>T		intron_variant	Intron 6 of 6		NM_001258282.3	ENSP00000513694.1

Frequencies

GnomAD3 genomes AF: 0.0981 AC: 14913 AN: 152078 Hom.: 730 Cov.: 32

Gnomad AFR AF: 0.0939

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.0833

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.0559

Gnomad SAS AF: 0.0882

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.0985

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

GnomAD4 genome AF: 0.0980 AC: 14917 AN: 152196 Hom.: 731 Cov.: 32 AF XY: 0.0962 AC XY: 7161 AN XY: 74414

African (AFR) AF: 0.0939 AC: 3898 AN: 41510

American (AMR) AF: 0.0831 AC: 1270 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 401 AN: 3466

East Asian (EAS) AF: 0.0560 AC: 290 AN: 5180

South Asian (SAS) AF: 0.0873 AC: 421 AN: 4824

European-Finnish (FIN) AF: 0.110 AC: 1169 AN: 10612

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7200 AN: 68008

Other (OTH) AF: 0.0974 AC: 206 AN: 2114

Alfa AF: 0.106 Hom.: 98

Bravo AF: 0.0954

Asia WGS AF: 0.0630 AC: 218 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.3
DANN	Benign	0.74
PhyloP100		0.12
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: rs10968280; hg19: chr9-28011645;