9-28983840-C-T

Variant names:

• chr9-28983840-C-T
• rs1813345
• NM_001258282.3:c.-491-35926G>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.-491-35926G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.65 in 151,642 control chromosomes in the GnomAD database, including 32,648 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 0.65 (32648 hom., cov: 31)
• Consequence: LINGO2 NM_001258282.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0460
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.712 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LINGO2	NM_001258282.3	c.-491-35926G>A		intron_variant	Intron 1 of 6	ENST00000698399.1	NP_001245211.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LINGO2	ENST00000698399.1	c.-491-35926G>A		intron_variant	Intron 1 of 6		NM_001258282.3	ENSP00000513694.1
LINGO2	ENST00000698401.1	c.-861-35926G>A		intron_variant	Intron 1 of 7			ENSP00000513696.1
LINGO2	ENST00000698402.1	c.-646-35926G>A		intron_variant	Intron 1 of 7			ENSP00000513697.1
LINGO2	ENST00000698404.1	c.-602-35926G>A		intron_variant	Intron 1 of 8			ENSP00000513699.1

Frequencies

GnomAD3 genomes AF: 0.651 AC: 98573 AN: 151524 Hom.: 32633 Cov.: 31

Gnomad AFR AF: 0.514

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.669

Gnomad ASJ AF: 0.796

Gnomad EAS AF: 0.585

Gnomad SAS AF: 0.635

Gnomad FIN AF: 0.724

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.717

Gnomad OTH AF: 0.671

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

GnomAD4 genome AF: 0.650 AC: 98634 AN: 151642 Hom.: 32648 Cov.: 31 AF XY: 0.649 AC XY: 48102 AN XY: 74094

African (AFR) AF: 0.514 AC: 21265 AN: 41390

American (AMR) AF: 0.669 AC: 10160 AN: 15186

Ashkenazi Jewish (ASJ) AF: 0.796 AC: 2761 AN: 3470

East Asian (EAS) AF: 0.585 AC: 3000 AN: 5128

South Asian (SAS) AF: 0.636 AC: 3071 AN: 4828

European-Finnish (FIN) AF: 0.724 AC: 7633 AN: 10548

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.717 AC: 48619 AN: 67790

Other (OTH) AF: 0.666 AC: 1395 AN: 2096

Alfa AF: 0.589 Hom.: 1907

Bravo AF: 0.640

Asia WGS AF: 0.588 AC: 2043 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.99
DANN	Benign	0.37
PhyloP100		-0.046

Splicing

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

Other links and lift over

dbSNP: rs1813345; hg19: chr9-28983838;