rs10968562

Positions:

• chr9-28402045-A-G

Variant summary

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

The NM_001258282.3(LINGO2):​c.-227-29177T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,058 control chromosomes in the GnomAD database, including 2,380 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 (2380 hom., cov: 32)
• Consequence: LINGO2 NM_001258282.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0270

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LINGO2	NM_001258282.3	c.-227-29177T>C		intron_variant		ENST00000698399.1	NP_001245211.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LINGO2	ENST00000698399.1	c.-227-29177T>C		intron_variant			NM_001258282.3	ENSP00000513694	P1

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24544 AN: 151938 Hom.: 2368 Cov.: 32

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.0484

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0994

Gnomad OTH AF: 0.133

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

GnomAD4 genome AF: 0.162 AC: 24599 AN: 152058 Hom.: 2380 Cov.: 32 AF XY: 0.168 AC XY: 12504 AN XY: 74312

Gnomad4 AFR AF: 0.242

Gnomad4 AMR AF: 0.201

Gnomad4 ASJ AF: 0.0484

Gnomad4 EAS AF: 0.180

Gnomad4 SAS AF: 0.209

Gnomad4 FIN AF: 0.208

Gnomad4 NFE AF: 0.0994

Gnomad4 OTH AF: 0.134

Alfa AF: 0.125 Hom.: 1309

Bravo AF: 0.167

Asia WGS AF: 0.210 AC: 727 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	4.1
DANN	Benign	0.79

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: rs10968562; hg19: chr9-28402043;