9-28478307-A-T

Variant names:

• chr9-28478307-A-T
• rs1412229
• NM_001258282.3:c.-313-2282T>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.-313-2282T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 151,946 control chromosomes in the GnomAD database, including 18,986 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 0.48 (18986 hom., cov: 32)
• Consequence: LINGO2 NM_001258282.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.82
• Publications: 5 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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LINGO2	NM_001258282.3	c.-313-2282T>A		intron_variant	Intron 3 of 6	ENST00000698399.1	NP_001245211.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LINGO2	ENST00000698399.1	c.-313-2282T>A		intron_variant	Intron 3 of 6		NM_001258282.3	ENSP00000513694.1

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72602 AN: 151828 Hom.: 18978 Cov.: 32

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.815

Gnomad AMR AF: 0.555

Gnomad ASJ AF: 0.590

Gnomad EAS AF: 0.428

Gnomad SAS AF: 0.529

Gnomad FIN AF: 0.549

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.570

Gnomad OTH AF: 0.518

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

GnomAD4 genome AF: 0.478 AC: 72642 AN: 151946 Hom.: 18986 Cov.: 32 AF XY: 0.481 AC XY: 35757 AN XY: 74282

African (AFR) AF: 0.261 AC: 10831 AN: 41462

American (AMR) AF: 0.555 AC: 8466 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.590 AC: 2043 AN: 3464

East Asian (EAS) AF: 0.429 AC: 2219 AN: 5168

South Asian (SAS) AF: 0.527 AC: 2544 AN: 4824

European-Finnish (FIN) AF: 0.549 AC: 5804 AN: 10572

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.570 AC: 38707 AN: 67882

Other (OTH) AF: 0.520 AC: 1098 AN: 2112

Alfa AF: 0.501 Hom.: 2505

Bravo AF: 0.468

Asia WGS AF: 0.496 AC: 1723 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.8
DANN	Benign	0.58
PhyloP100		-2.8
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: rs1412229; hg19: chr9-28478305;