chr9-28415565-G-T

Variant names:

• chr9-28415565-G-T
• rs12003487
• NM_001258282.3:c.-227-42697C>A

Variant summary

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

The NM_001258282.3(LINGO2):​c.-227-42697C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 152,012 control chromosomes in the GnomAD database, including 7,695 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 0.29 (7695 hom., cov: 32)
• Consequence: LINGO2 NM_001258282.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LINGO2	NM_001258282.3	c.-227-42697C>A		intron_variant	Intron 4 of 6	ENST00000698399.1	NP_001245211.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LINGO2	ENST00000698399.1	c.-227-42697C>A		intron_variant	Intron 4 of 6		NM_001258282.3	ENSP00000513694.1

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44665 AN: 151894 Hom.: 7696 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.429

Gnomad EAS AF: 0.0694

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.320

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

GnomAD4 genome AF: 0.294 AC: 44661 AN: 152012 Hom.: 7695 Cov.: 32 AF XY: 0.292 AC XY: 21693 AN XY: 74304

African (AFR) AF: 0.134 AC: 5542 AN: 41468

American (AMR) AF: 0.369 AC: 5630 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.429 AC: 1487 AN: 3468

East Asian (EAS) AF: 0.0695 AC: 359 AN: 5164

South Asian (SAS) AF: 0.285 AC: 1371 AN: 4818

European-Finnish (FIN) AF: 0.324 AC: 3421 AN: 10554

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.378 AC: 25693 AN: 67964

Other (OTH) AF: 0.322 AC: 682 AN: 2116

Alfa AF: 0.180 Hom.: 419

Bravo AF: 0.288

Asia WGS AF: 0.191 AC: 666 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.11
DANN	Benign	0.63
PhyloP100		-1.6
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: rs12003487; hg19: chr9-28415563;