rs10968460

Variant names:

• chr9-28295374-A-G
• rs10968460
• NM_001258282.3:c.-194-8T>C

Your query was ambiguous. Multiple possible variants found:

• chr9-28295374-A-G
• chr9-28295374-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001258282.3(LINGO2):​c.-194-8T>C variant causes a splice region, 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, intron
• Scores: Splicing: ADA: 0.00004599
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.54
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001258282.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINGO2	NM_001258282.3	MANE Select	c.-194-8T>C		splice_region intron	N/A	NP_001245211.1
	LINGO2	NM_001354574.2		c.-194-8T>C		splice_region intron	N/A	NP_001341503.1
	LINGO2	NM_001354575.2		c.-194-8T>C		splice_region intron	N/A	NP_001341504.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINGO2	ENST00000698399.1	MANE Select	c.-194-8T>C		splice_region intron	N/A	ENSP00000513694.1
	LINGO2	ENST00000379992.6	TSL:5	c.-245-8T>C		splice_region intron	N/A	ENSP00000369328.1
	LINGO2	ENST00000698400.1		c.-409-8T>C		splice_region intron	N/A	ENSP00000513695.1

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

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.0968 AC: 43 AN: 444

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 10

Other (OTH) AF: 0.00 AC: 0 AN: 6

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

African (AFR) AF: 0.0501 AC: 2080 AN: 41524

American (AMR) AF: 0.104 AC: 1592 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.0663 AC: 230 AN: 3470

East Asian (EAS) AF: 0.386 AC: 1976 AN: 5122

South Asian (SAS) AF: 0.0869 AC: 419 AN: 4822

European-Finnish (FIN) AF: 0.0932 AC: 986 AN: 10580

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0517 AC: 3517 AN: 67986

Other (OTH) AF: 0.0733 AC: 155 AN: 2114

Alfa AF: 0.0387 Hom.: 32

Bravo AF: 0.0758

Asia WGS AF: 0.219 AC: 760 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	6.8
DANN	Benign	0.67
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10968460; hg19: chr9-28295372;