9-28323675-C-T

Variant names:

• chr9-28323675-C-T
• rs953924
• NM_001258282.3:c.-194-28309G>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.-194-28309G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 152,068 control chromosomes in the GnomAD database, including 1,101 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 0.10 (1101 hom., cov: 32)
• Consequence: LINGO2 NM_001258282.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.706
• Publications: 2 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=-0.61).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LINGO2	NM_001258282.3	c.-194-28309G>A		intron_variant	Intron 5 of 6	ENST00000698399.1	NP_001245211.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LINGO2	ENST00000698399.1	c.-194-28309G>A		intron_variant	Intron 5 of 6		NM_001258282.3	ENSP00000513694.1

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15352 AN: 151950 Hom.: 1097 Cov.: 32

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0790

Gnomad ASJ AF: 0.0631

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.0696

Gnomad FIN AF: 0.0522

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0505

Gnomad OTH AF: 0.0805

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

GnomAD4 genome AF: 0.101 AC: 15381 AN: 152068 Hom.: 1101 Cov.: 32 AF XY: 0.100 AC XY: 7435 AN XY: 74344

African (AFR) AF: 0.204 AC: 8466 AN: 41436

American (AMR) AF: 0.0793 AC: 1210 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.0631 AC: 219 AN: 3472

East Asian (EAS) AF: 0.186 AC: 960 AN: 5170

South Asian (SAS) AF: 0.0699 AC: 337 AN: 4824

European-Finnish (FIN) AF: 0.0522 AC: 553 AN: 10604

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0505 AC: 3432 AN: 67982

Other (OTH) AF: 0.0806 AC: 170 AN: 2110

Alfa AF: 0.0380 Hom.: 57

Bravo AF: 0.111

Asia WGS AF: 0.129 AC: 449 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	2.5
DANN	Benign	0.81
PhyloP100		-0.71
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: rs953924; hg19: chr9-28323673;