rs4880001

Variant names:

• chr9-28011385-T-C
• rs4880001
• NM_001258282.3:c.-35-60679A>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.-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
• 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 (NFE) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001258282.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINGO2	NM_001258282.3	MANE Select	c.-35-60679A>G		intron	N/A	NP_001245211.1
	LINGO2	NM_001354574.2		c.-35-60679A>G		intron	N/A	NP_001341503.1
	LINGO2	NM_001354575.2		c.-35-60679A>G		intron	N/A	NP_001341504.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINGO2	ENST00000698399.1	MANE Select	c.-35-60679A>G		intron	N/A	ENSP00000513694.1
	LINGO2	ENST00000379992.6	TSL:5	c.-36+970A>G		intron	N/A	ENSP00000369328.1
	LINGO2	ENST00000698400.1		c.-36+14874A>G		intron	N/A	ENSP00000513695.1

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

African (AFR) AF: 0.146 AC: 6044 AN: 41468

American (AMR) AF: 0.337 AC: 5147 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.331 AC: 1149 AN: 3468

East Asian (EAS) AF: 0.0211 AC: 109 AN: 5176

South Asian (SAS) AF: 0.206 AC: 988 AN: 4806

European-Finnish (FIN) AF: 0.411 AC: 4343 AN: 10560

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.394 AC: 26787 AN: 67960

Other (OTH) AF: 0.286 AC: 604 AN: 2112

Alfa AF: 0.352 Hom.: 31806

Bravo AF: 0.285

Asia WGS AF: 0.134 AC: 468 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.57
DANN	Benign	0.73
PhyloP100		-0.66
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: rs4880001; hg19: chr9-28011383; COSMIC: COSV58063768;