chr9-28817959-T-C

Variant names:

• chr9-28817959-T-C
• rs1389728
• NM_001258282.3:c.-395+129859A>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.-395+129859A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0989 in 152,194 control chromosomes in the GnomAD database, including 814 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 0.099 (814 hom., cov: 32)
• Consequence: LINGO2 NM_001258282.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.306
• Publications: 3 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LINGO2	NM_001258282.3	c.-395+129859A>G		intron_variant	Intron 2 of 6	ENST00000698399.1	NP_001245211.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LINGO2	ENST00000698399.1	c.-395+129859A>G		intron_variant	Intron 2 of 6		NM_001258282.3	ENSP00000513694.1
LINGO2	ENST00000698401.1	c.-765+129859A>G		intron_variant	Intron 2 of 7			ENSP00000513696.1
LINGO2	ENST00000698402.1	c.-550+129859A>G		intron_variant	Intron 2 of 7			ENSP00000513697.1
LINGO2	ENST00000698404.1	c.-506+129859A>G		intron_variant	Intron 2 of 8			ENSP00000513699.1

Frequencies

GnomAD3 genomes AF: 0.0989 AC: 15042 AN: 152076 Hom.: 815 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0843

Gnomad ASJ AF: 0.0660

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.0894

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0848

Gnomad OTH AF: 0.0869

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

GnomAD4 genome AF: 0.0989 AC: 15052 AN: 152194 Hom.: 814 Cov.: 32 AF XY: 0.101 AC XY: 7538 AN XY: 74428

African (AFR) AF: 0.123 AC: 5104 AN: 41498

American (AMR) AF: 0.0845 AC: 1291 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0660 AC: 229 AN: 3472

East Asian (EAS) AF: 0.105 AC: 544 AN: 5188

South Asian (SAS) AF: 0.0893 AC: 431 AN: 4826

European-Finnish (FIN) AF: 0.137 AC: 1449 AN: 10596

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.0848 AC: 5771 AN: 68016

Other (OTH) AF: 0.0859 AC: 181 AN: 2106

Alfa AF: 0.0865 Hom.: 2302

Bravo AF: 0.0950

Asia WGS AF: 0.0930 AC: 323 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.6
DANN	Benign	0.65
PhyloP100		-0.31

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1389728; hg19: chr9-28817957;