rs12341535

chr9-28663044-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.87).
• 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/exons	MANE	UniProt
LINGO2	NM_001258282.3	c.-314+7156A>G		intron_variant		ENST00000698399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LINGO2	ENST00000698399.1	c.-314+7156A>G		intron_variant			NM_001258282.3	P1

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

Gnomad4 AFR AF: 0.377

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.0357

Gnomad4 SAS AF: 0.0731

Gnomad4 FIN AF: 0.0933

Gnomad4 NFE AF: 0.0944

Gnomad4 OTH AF: 0.171

Alfa AF: 0.112 Hom.: 1150

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs12341535; hg19: chr9-28663042;