rs12339229

chr9-28093234-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001258282.3(LINGO2):c.-35-142528G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.064 in 152,112 control chromosomes in the GnomAD database, including 489 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 0.064 (489 hom., cov: 32)
• Consequence: LINGO2 NM_001258282.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.346

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LINGO2	NM_001258282.3	c.-35-142528G>A		intron_variant		ENST00000698399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LINGO2	ENST00000698399.1	c.-35-142528G>A		intron_variant			NM_001258282.3	P1

Frequencies

GnomAD3 genomes AF: 0.0638 AC: 9696 AN: 151994 Hom.: 485 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0456

Gnomad ASJ AF: 0.0268

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00704

Gnomad FIN AF: 0.0122

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0399

Gnomad OTH AF: 0.0600

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

GnomAD4 genome AF: 0.0640 AC: 9730 AN: 152112 Hom.: 489 Cov.: 32 AF XY: 0.0622 AC XY: 4625 AN XY: 74372

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.0455

Gnomad4 ASJ AF: 0.0268

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00663

Gnomad4 FIN AF: 0.0122

Gnomad4 NFE AF: 0.0399

Gnomad4 OTH AF: 0.0594

Alfa AF: 0.0526 Hom.: 127

Bravo AF: 0.0710

Asia WGS AF: 0.0140 AC: 48 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
Cadd	Benign	13
Dann	Benign	0.49

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

Publications

LitVar

Other links and lift over

dbSNP: rs12339229; hg19: chr9-28093232;