9-28181087-C-T

Position:

• chr9-28181087-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.-36+114121G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.623 in 151,814 control chromosomes in the GnomAD database, including 29,667 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 0.62 (29667 hom., cov: 31)
• Consequence: LINGO2 NM_001258282.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0900

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LINGO2	NM_001258282.3	c.-36+114121G>A		intron_variant		ENST00000698399.1	NP_001245211.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LINGO2	ENST00000698399.1	c.-36+114121G>A		intron_variant			NM_001258282.3	ENSP00000513694	P1

Frequencies

GnomAD3 genomes AF: 0.623 AC: 94495 AN: 151696 Hom.: 29649 Cov.: 31

Gnomad AFR AF: 0.615

Gnomad AMI AF: 0.669

Gnomad AMR AF: 0.668

Gnomad ASJ AF: 0.604

Gnomad EAS AF: 0.515

Gnomad SAS AF: 0.385

Gnomad FIN AF: 0.604

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.646

Gnomad OTH AF: 0.627

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

GnomAD4 genome AF: 0.623 AC: 94567 AN: 151814 Hom.: 29667 Cov.: 31 AF XY: 0.615 AC XY: 45640 AN XY: 74178

Gnomad4 AFR AF: 0.615

Gnomad4 AMR AF: 0.668

Gnomad4 ASJ AF: 0.604

Gnomad4 EAS AF: 0.514

Gnomad4 SAS AF: 0.384

Gnomad4 FIN AF: 0.604

Gnomad4 NFE AF: 0.646

Gnomad4 OTH AF: 0.628

Alfa AF: 0.632 Hom.: 40964

Bravo AF: 0.634

Asia WGS AF: 0.484 AC: 1681 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.7
DANN	Benign	0.43

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: rs1319535; hg19: chr9-28181085; COSMIC: COSV66143344;