rs981045

chr9-28084989-A-G

Variant summary

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

The NM_001258282.3(LINGO2):c.-35-134283T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 151,856 control chromosomes in the GnomAD database, including 23,363 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 0.55 (23363 hom., cov: 31)
• Consequence: LINGO2 NM_001258282.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.226

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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LINGO2	NM_001258282.3	c.-35-134283T>C		intron_variant		ENST00000698399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LINGO2	ENST00000698399.1	c.-35-134283T>C		intron_variant			NM_001258282.3	P1

Frequencies

GnomAD3 genomes AF: 0.548 AC: 83190 AN: 151736 Hom.: 23364 Cov.: 31

Gnomad AFR AF: 0.413

Gnomad AMI AF: 0.508

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.639

Gnomad EAS AF: 0.683

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.557

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.610

Gnomad OTH AF: 0.576

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

GnomAD4 genome AF: 0.548 AC: 83216 AN: 151856 Hom.: 23363 Cov.: 31 AF XY: 0.548 AC XY: 40669 AN XY: 74198

Gnomad4 AFR AF: 0.412

Gnomad4 AMR AF: 0.561

Gnomad4 ASJ AF: 0.639

Gnomad4 EAS AF: 0.683

Gnomad4 SAS AF: 0.570

Gnomad4 FIN AF: 0.557

Gnomad4 NFE AF: 0.610

Gnomad4 OTH AF: 0.572

Alfa AF: 0.575 Hom.: 3223

Bravo AF: 0.541

Asia WGS AF: 0.591 AC: 2052 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	2.3
Dann	Benign	0.56

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: rs981045; hg19: chr9-28084987;