chr9-28492293-G-C

Position:

• chr9-28492293-G-C

Variant summary

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

The NM_001258282.3(LINGO2):​c.-313-16268C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0274 in 152,060 control chromosomes in the GnomAD database, including 212 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 0.027 (212 hom., cov: 33)
• Consequence: LINGO2 NM_001258282.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0530

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LINGO2	NM_001258282.3	c.-313-16268C>G		intron_variant		ENST00000698399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LINGO2	ENST00000698399.1	c.-313-16268C>G		intron_variant			NM_001258282.3	P1

Frequencies

GnomAD3 genomes AF: 0.0273 AC: 4148 AN: 151942 Hom.: 211 Cov.: 33

Gnomad AFR AF: 0.0438

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0448

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.0782

Gnomad FIN AF: 0.00274

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00263

Gnomad OTH AF: 0.0287

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

GnomAD4 genome AF: 0.0274 AC: 4165 AN: 152060 Hom.: 212 Cov.: 33 AF XY: 0.0288 AC XY: 2137 AN XY: 74328

Gnomad4 AFR AF: 0.0439

Gnomad4 AMR AF: 0.0453

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.193

Gnomad4 SAS AF: 0.0789

Gnomad4 FIN AF: 0.00274

Gnomad4 NFE AF: 0.00263

Gnomad4 OTH AF: 0.0298

Alfa AF: 0.0166 Hom.: 9

Bravo AF: 0.0325

Asia WGS AF: 0.121 AC: 419 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.9
DANN	Benign	0.75

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: rs10491887; hg19: chr9-28492291;