NM_001258282.3:c.-395+127009T>C

Variant names:

• chr9-28820809-A-G
• rs969715
• NM_001258282.3:c.-395+127009T>C

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+127009T>C 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 152,220 control chromosomes in the GnomAD database, including 904 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 (904 hom., cov: 33)
• Consequence: LINGO2 NM_001258282.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.54
• 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=-0.47).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LINGO2	NM_001258282.3	c.-395+127009T>C		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+127009T>C		intron_variant	Intron 2 of 6		NM_001258282.3	ENSP00000513694.1
LINGO2	ENST00000698401.1	c.-765+127009T>C		intron_variant	Intron 2 of 7			ENSP00000513696.1
LINGO2	ENST00000698402.1	c.-550+127009T>C		intron_variant	Intron 2 of 7			ENSP00000513697.1
LINGO2	ENST00000698404.1	c.-506+127009T>C		intron_variant	Intron 2 of 8			ENSP00000513699.1

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15355 AN: 152102 Hom.: 903 Cov.: 33

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0837

Gnomad ASJ AF: 0.0608

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.0894

Gnomad FIN AF: 0.0978

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0760

Gnomad OTH AF: 0.0870

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

GnomAD4 genome AF: 0.101 AC: 15372 AN: 152220 Hom.: 904 Cov.: 33 AF XY: 0.102 AC XY: 7574 AN XY: 74420

African (AFR) AF: 0.156 AC: 6475 AN: 41526

American (AMR) AF: 0.0838 AC: 1282 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0608 AC: 211 AN: 3472

East Asian (EAS) AF: 0.104 AC: 540 AN: 5170

South Asian (SAS) AF: 0.0893 AC: 431 AN: 4828

European-Finnish (FIN) AF: 0.0978 AC: 1037 AN: 10608

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0760 AC: 5167 AN: 68004

Other (OTH) AF: 0.0861 AC: 182 AN: 2114

Alfa AF: 0.0534 Hom.: 88

Bravo AF: 0.101

Asia WGS AF: 0.0940 AC: 325 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	15
DANN	Benign	0.81
PhyloP100		1.5

Splicing

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

Other links and lift over

dbSNP: rs969715; hg19: chr9-28820807;