9-28415565-G-T

Position:

• chr9-28415565-G-T

Variant summary

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

The NM_001258282.3(LINGO2):​c.-227-42697C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 152,012 control chromosomes in the GnomAD database, including 7,695 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 0.29 (7695 hom., cov: 32)
• Consequence: LINGO2 NM_001258282.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56

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 (NFE) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LINGO2	NM_001258282.3	c.-227-42697C>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.-227-42697C>A		intron_variant			NM_001258282.3	ENSP00000513694.1

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44665 AN: 151894 Hom.: 7696 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.429

Gnomad EAS AF: 0.0694

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.320

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

GnomAD4 genome AF: 0.294 AC: 44661 AN: 152012 Hom.: 7695 Cov.: 32 AF XY: 0.292 AC XY: 21693 AN XY: 74304

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.369

Gnomad4 ASJ AF: 0.429

Gnomad4 EAS AF: 0.0695

Gnomad4 SAS AF: 0.285

Gnomad4 FIN AF: 0.324

Gnomad4 NFE AF: 0.378

Gnomad4 OTH AF: 0.322

Alfa AF: 0.182 Hom.: 414

Bravo AF: 0.288

Asia WGS AF: 0.191 AC: 666 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.11
DANN	Benign	0.63

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: rs12003487; hg19: chr9-28415563;