rs4880001

chr9-28011385-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.-35-60679A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 152,038 control chromosomes in the GnomAD database, including 7,931 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 0.30 (7931 hom., cov: 32)
• Consequence: LINGO2 NM_001258282.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.658

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LINGO2	NM_001258282.3	c.-35-60679A>G		intron_variant		ENST00000698399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LINGO2	ENST00000698399.1	c.-35-60679A>G		intron_variant			NM_001258282.3	P1

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45527 AN: 151920 Hom.: 7932 Cov.: 32

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.0212

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.411

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.290

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

GnomAD4 genome AF: 0.299 AC: 45527 AN: 152038 Hom.: 7931 Cov.: 32 AF XY: 0.297 AC XY: 22075 AN XY: 74316

Gnomad4 AFR AF: 0.146

Gnomad4 AMR AF: 0.337

Gnomad4 ASJ AF: 0.331

Gnomad4 EAS AF: 0.0211

Gnomad4 SAS AF: 0.206

Gnomad4 FIN AF: 0.411

Gnomad4 NFE AF: 0.394

Gnomad4 OTH AF: 0.286

Alfa AF: 0.360 Hom.: 14089

Bravo AF: 0.285

Asia WGS AF: 0.134 AC: 468 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	0.57
Dann	Benign	0.73

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: rs4880001; hg19: chr9-28011383; COSMIC: COSV58063768;