9-28719761-G-C

Position:

• chr9-28719761-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.-394-49481C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 151,720 control chromosomes in the GnomAD database, including 4,859 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 0.24 (4859 hom., cov: 32)
• Consequence: LINGO2 NM_001258282.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0580

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LINGO2	NM_001258282.3	c.-394-49481C>G		intron_variant		ENST00000698399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LINGO2	ENST00000698399.1	c.-394-49481C>G		intron_variant			NM_001258282.3	P1
LINGO2	ENST00000698401.1	c.-764-49481C>G		intron_variant				P1
LINGO2	ENST00000698402.1	c.-549-49481C>G		intron_variant				P1
LINGO2	ENST00000698404.1	c.-505-49481C>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36781 AN: 151606 Hom.: 4863 Cov.: 32

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.288

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.325

Gnomad MID AF: 0.201

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.265

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

GnomAD4 genome AF: 0.242 AC: 36779 AN: 151720 Hom.: 4859 Cov.: 32 AF XY: 0.250 AC XY: 18495 AN XY: 74112

Gnomad4 AFR AF: 0.154

Gnomad4 AMR AF: 0.377

Gnomad4 ASJ AF: 0.166

Gnomad4 EAS AF: 0.288

Gnomad4 SAS AF: 0.270

Gnomad4 FIN AF: 0.325

Gnomad4 NFE AF: 0.253

Gnomad4 OTH AF: 0.262

Alfa AF: 0.133 Hom.: 277

Bravo AF: 0.242

Asia WGS AF: 0.290 AC: 1006 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.1
DANN	Benign	0.80

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6476092; hg19: chr9-28719759;