NM_001258282.3:c.-195+1084T>G

Variant names:

• chr9-28371752-A-C
• rs1331866
• NM_001258282.3:c.-195+1084T>G

Variant summary

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

The NM_001258282.3(LINGO2):​c.-195+1084T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.784 in 152,128 control chromosomes in the GnomAD database, including 47,983 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 0.78 (47983 hom., cov: 32)
• Consequence: LINGO2 NM_001258282.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.74
• Publications: 1 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=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.856 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.-195+1084T>G		intron	N/A	NP_001245211.1
	LINGO2	NM_001354574.2		c.-194-76386T>G		intron	N/A	NP_001341503.1
	LINGO2	NM_001354575.2		c.-195+1084T>G		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.-195+1084T>G		intron	N/A	ENSP00000513694.1
	LINGO2	ENST00000379992.6	TSL:5	c.-246+1084T>G		intron	N/A	ENSP00000369328.1
	LINGO2	ENST00000698400.1		c.-410+1084T>G		intron	N/A	ENSP00000513695.1

Frequencies

GnomAD3 genomes AF: 0.784 AC: 119157 AN: 152010 Hom.: 47938 Cov.: 32

Gnomad AFR AF: 0.589

Gnomad AMI AF: 0.945

Gnomad AMR AF: 0.855

Gnomad ASJ AF: 0.831

Gnomad EAS AF: 0.752

Gnomad SAS AF: 0.874

Gnomad FIN AF: 0.874

Gnomad MID AF: 0.886

Gnomad NFE AF: 0.862

Gnomad OTH AF: 0.825

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

GnomAD4 genome AF: 0.784 AC: 119260 AN: 152128 Hom.: 47983 Cov.: 32 AF XY: 0.786 AC XY: 58429 AN XY: 74380

African (AFR) AF: 0.589 AC: 24432 AN: 41452

American (AMR) AF: 0.855 AC: 13062 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.831 AC: 2886 AN: 3472

East Asian (EAS) AF: 0.752 AC: 3888 AN: 5168

South Asian (SAS) AF: 0.876 AC: 4215 AN: 4814

European-Finnish (FIN) AF: 0.874 AC: 9267 AN: 10600

Middle Eastern (MID) AF: 0.901 AC: 265 AN: 294

European-Non Finnish (NFE) AF: 0.862 AC: 58637 AN: 68020

Other (OTH) AF: 0.827 AC: 1746 AN: 2112

Alfa AF: 0.760 Hom.: 2682

Bravo AF: 0.777

Asia WGS AF: 0.823 AC: 2863 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.23
DANN	Benign	0.34
PhyloP100		-2.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1331866; hg19: chr9-28371750; COSMIC: COSV66149550;