rs10968460

chr9-28295374-A-Gchr9-28295374-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.-194-8T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0723 in 152,548 control chromosomes in the GnomAD database, including 722 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.072 (721 hom., cov: 32)
  • Exomes 𝑓: 0.093 (1 hom.)
• Consequence: LINGO2 NM_001258282.3 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00004599
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.54

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=-0.55).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LINGO2	NM_001258282.3	c.-194-8T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000698399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LINGO2	ENST00000698399.1	c.-194-8T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NM_001258282.3	P1

Frequencies

GnomAD3 genomes AF: 0.0722 AC: 10966 AN: 151968 Hom.: 715 Cov.: 32

Gnomad AFR AF: 0.0502

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.0663

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.0870

Gnomad FIN AF: 0.0932

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0517

Gnomad OTH AF: 0.0703

GnomAD4 exome AF: 0.0931 AC: 43 AN: 462 Hom.: 1 Cov.: 0 AF XY: 0.0926 AC XY: 25 AN XY: 270

Gnomad4 AFR exome AF: 0.00

Gnomad4 FIN exome AF: 0.0968

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0722 AC: 10984 AN: 152086 Hom.: 721 Cov.: 32 AF XY: 0.0764 AC XY: 5682 AN XY: 74328

Gnomad4 AFR AF: 0.0501

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.0663

Gnomad4 EAS AF: 0.386

Gnomad4 SAS AF: 0.0869

Gnomad4 FIN AF: 0.0932

Gnomad4 NFE AF: 0.0517

Gnomad4 OTH AF: 0.0733

Alfa AF: 0.0384 Hom.: 31

Bravo AF: 0.0758

Asia WGS AF: 0.219 AC: 760 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
Cadd	Benign	6.8
Dann	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000046
dbscSNV1_RF	Benign	0.0060
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: rs10968460; hg19: chr9-28295372;