rs7046685

Variant names:

• chr9-28659145-A-G
• rs7046685
• NM_001258282.3:c.-314+11055T>C

Variant summary

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

The NM_001258282.3(LINGO2):​c.-314+11055T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 152,058 control chromosomes in the GnomAD database, including 3,987 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 0.18 (3987 hom., cov: 32)
• Consequence: LINGO2 NM_001258282.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0930
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.398 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINGO2	NM_001258282.3	MANE Select	c.-314+11055T>C		intron	N/A	NP_001245211.1	Q7L985
	LINGO2	NM_001354574.2		c.-281+11055T>C		intron	N/A	NP_001341503.1	Q7L985
	LINGO2	NM_001354575.2		c.-314+11055T>C		intron	N/A	NP_001341504.1	Q7L985

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINGO2	ENST00000698399.1	MANE Select	c.-314+11055T>C		intron	N/A	ENSP00000513694.1	Q7L985
	LINGO2	ENST00000379992.6	TSL:5	c.-365+11055T>C		intron	N/A	ENSP00000369328.1	Q7L985
	LINGO2	ENST00000698400.1		c.-529+11055T>C		intron	N/A	ENSP00000513695.1	Q7L985

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27548 AN: 151942 Hom.: 3955 Cov.: 32

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.0357

Gnomad SAS AF: 0.0732

Gnomad FIN AF: 0.0934

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.0947

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.182 AC: 27637 AN: 152058 Hom.: 3987 Cov.: 32 AF XY: 0.179 AC XY: 13272 AN XY: 74332

African (AFR) AF: 0.403 AC: 16710 AN: 41470

American (AMR) AF: 0.137 AC: 2095 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 370 AN: 3470

East Asian (EAS) AF: 0.0354 AC: 183 AN: 5172

South Asian (SAS) AF: 0.0733 AC: 352 AN: 4800

European-Finnish (FIN) AF: 0.0934 AC: 989 AN: 10586

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.0947 AC: 6434 AN: 67970

Other (OTH) AF: 0.176 AC: 371 AN: 2110

Alfa AF: 0.112 Hom.: 2071

Bravo AF: 0.194

Asia WGS AF: 0.0910 AC: 315 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.9
DANN	Benign	0.75
PhyloP100		0.093
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: rs7046685; hg19: chr9-28659143;