rs824248

Positions:

• chr9-28772702-A-T

Variant summary

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

The NM_001258282.3(LINGO2):​c.-394-102422T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 152,080 control chromosomes in the GnomAD database, including 4,284 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 0.23 (4284 hom., cov: 32)
• Consequence: LINGO2 NM_001258282.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.36

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LINGO2	NM_001258282.3	c.-394-102422T>A		intron_variant		ENST00000698399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LINGO2	ENST00000698399.1	c.-394-102422T>A		intron_variant			NM_001258282.3	P1
LINGO2	ENST00000698401.1	c.-764-102422T>A		intron_variant				P1
LINGO2	ENST00000698402.1	c.-549-102422T>A		intron_variant				P1
LINGO2	ENST00000698404.1	c.-505-102422T>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35504 AN: 151962 Hom.: 4269 Cov.: 32

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.115

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.234 AC: 35551 AN: 152080 Hom.: 4284 Cov.: 32 AF XY: 0.236 AC XY: 17521 AN XY: 74344

Gnomad4 AFR AF: 0.215

Gnomad4 AMR AF: 0.247

Gnomad4 ASJ AF: 0.175

Gnomad4 EAS AF: 0.392

Gnomad4 SAS AF: 0.236

Gnomad4 FIN AF: 0.265

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.211

Alfa AF: 0.223 Hom.: 493

Bravo AF: 0.234

Asia WGS AF: 0.307 AC: 1065 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	16
DANN	Benign	0.81

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs824248; hg19: chr9-28772700;