rs10968562

Variant names:

• chr9-28402045-A-G
• rs10968562
• NM_001258282.3:c.-227-29177T>C

Variant summary

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

The NM_001258282.3(LINGO2):​c.-227-29177T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,058 control chromosomes in the GnomAD database, including 2,380 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 0.16 (2380 hom., cov: 32)
• Consequence: LINGO2 NM_001258282.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0270
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LINGO2	NM_001258282.3	c.-227-29177T>C		intron_variant	Intron 4 of 6	ENST00000698399.1	NP_001245211.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LINGO2	ENST00000698399.1	c.-227-29177T>C		intron_variant	Intron 4 of 6		NM_001258282.3	ENSP00000513694.1

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24544 AN: 151938 Hom.: 2368 Cov.: 32

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.0484

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0994

Gnomad OTH AF: 0.133

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

GnomAD4 genome AF: 0.162 AC: 24599 AN: 152058 Hom.: 2380 Cov.: 32 AF XY: 0.168 AC XY: 12504 AN XY: 74312

African (AFR) AF: 0.242 AC: 10036 AN: 41454

American (AMR) AF: 0.201 AC: 3066 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0484 AC: 168 AN: 3468

East Asian (EAS) AF: 0.180 AC: 926 AN: 5144

South Asian (SAS) AF: 0.209 AC: 1008 AN: 4826

European-Finnish (FIN) AF: 0.208 AC: 2196 AN: 10576

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0994 AC: 6760 AN: 68000

Other (OTH) AF: 0.134 AC: 284 AN: 2112

Alfa AF: 0.121 Hom.: 3220

Bravo AF: 0.167

Asia WGS AF: 0.210 AC: 727 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.1
DANN	Benign	0.79
PhyloP100		0.027
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: rs10968562; hg19: chr9-28402043;