rs12341535

Variant names:

• chr9-28663044-T-C
• rs12341535
• NM_001258282.3:c.-314+7156A>G

Variant summary

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

The NM_001258282.3(LINGO2):​c.-314+7156A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 152,120 control chromosomes in the GnomAD database, including 3,621 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 0.17 (3621 hom., cov: 32)
• Consequence: LINGO2 NM_001258282.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.181
• Publications: 1 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LINGO2	NM_001258282.3	c.-314+7156A>G		intron_variant	Intron 3 of 6	ENST00000698399.1	NP_001245211.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LINGO2	ENST00000698399.1	c.-314+7156A>G		intron_variant	Intron 3 of 6		NM_001258282.3	ENSP00000513694.1

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26419 AN: 152002 Hom.: 3589 Cov.: 32

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.0360

Gnomad SAS AF: 0.0731

Gnomad FIN AF: 0.0933

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.0944

Gnomad OTH AF: 0.171

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

GnomAD4 genome AF: 0.174 AC: 26506 AN: 152120 Hom.: 3621 Cov.: 32 AF XY: 0.171 AC XY: 12744 AN XY: 74368

African (AFR) AF: 0.377 AC: 15624 AN: 41474

American (AMR) AF: 0.136 AC: 2077 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 367 AN: 3466

East Asian (EAS) AF: 0.0357 AC: 185 AN: 5186

South Asian (SAS) AF: 0.0731 AC: 353 AN: 4826

European-Finnish (FIN) AF: 0.0933 AC: 990 AN: 10610

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.0944 AC: 6416 AN: 67982

Other (OTH) AF: 0.171 AC: 361 AN: 2112

Alfa AF: 0.123 Hom.: 1939

Bravo AF: 0.186

Asia WGS AF: 0.0900 AC: 314 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.69
DANN	Benign	0.56
PhyloP100		-0.18
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: rs12341535; hg19: chr9-28663042;