rs13296489

Positions:

• chr9-28372735-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001258282.3(LINGO2):​c.-195+101T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 152,494 control chromosomes in the GnomAD database, including 12,953 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 0.39 (12875 hom., cov: 34)
  • Exomes 𝑓: 0.60 (78 hom.)
• Consequence: LINGO2 NM_001258282.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.640

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LINGO2	NM_001258282.3	c.-195+101T>C		intron_variant		ENST00000698399.1	NP_001245211.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LINGO2	ENST00000698399.1	c.-195+101T>C		intron_variant			NM_001258282.3	ENSP00000513694	P1

Frequencies

GnomAD3 genomes AF: 0.391 AC: 59368 AN: 151946 Hom.: 12876 Cov.: 34

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.495

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.594

Gnomad MID AF: 0.372

Gnomad NFE AF: 0.470

Gnomad OTH AF: 0.407

GnomAD4 exome AF: 0.605 AC: 260 AN: 430 Hom.: 78 AF XY: 0.570 AC XY: 147 AN XY: 258

Gnomad4 FIN exome AF: 0.604

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.391 AC: 59383 AN: 152064 Hom.: 12875 Cov.: 34 AF XY: 0.394 AC XY: 29293 AN XY: 74334

Gnomad4 AFR AF: 0.218

Gnomad4 AMR AF: 0.390

Gnomad4 ASJ AF: 0.495

Gnomad4 EAS AF: 0.273

Gnomad4 SAS AF: 0.349

Gnomad4 FIN AF: 0.594

Gnomad4 NFE AF: 0.470

Gnomad4 OTH AF: 0.402

Alfa AF: 0.438 Hom.: 2170

Bravo AF: 0.374

Asia WGS AF: 0.275 AC: 953 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.2
DANN	Benign	0.94

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: rs13296489; hg19: chr9-28372733; COSMIC: COSV66124803;