rs2891316

Positions:

• chr9-28587996-G-A

Variant summary

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

The NM_001258282.3(LINGO2):​c.-314+82204C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 151,962 control chromosomes in the GnomAD database, including 2,272 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 0.16 (2272 hom., cov: 32)
• Consequence: LINGO2 NM_001258282.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00100

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]

LOC105376004 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LINGO2	NM_001258282.3	c.-314+82204C>T		intron_variant		ENST00000698399.1
LOC105376004	XR_001746641.2	n.445+8819G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LINGO2	ENST00000698399.1	c.-314+82204C>T		intron_variant			NM_001258282.3	P1

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23724 AN: 151842 Hom.: 2268 Cov.: 32

Gnomad AFR AF: 0.0765

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.0228

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.183

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

GnomAD4 genome AF: 0.156 AC: 23733 AN: 151962 Hom.: 2272 Cov.: 32 AF XY: 0.157 AC XY: 11686 AN XY: 74272

Gnomad4 AFR AF: 0.0766

Gnomad4 AMR AF: 0.277

Gnomad4 ASJ AF: 0.261

Gnomad4 EAS AF: 0.0226

Gnomad4 SAS AF: 0.120

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.181

Alfa AF: 0.184 Hom.: 1845

Bravo AF: 0.165

Asia WGS AF: 0.0910 AC: 316 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.9
DANN	Benign	0.56

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: rs2891316; hg19: chr9-28587994;