rs11793421

Variant names:

• chr9-28012157-T-C
• rs11793421
• NM_001258282.3:c.-35-61451A>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.-35-61451A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 152,134 control chromosomes in the GnomAD database, including 1,225 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 0.12 (1225 hom., cov: 32)
• Consequence: LINGO2 NM_001258282.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LINGO2	NM_001258282.3	c.-35-61451A>G		intron_variant	Intron 6 of 6	ENST00000698399.1	NP_001245211.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LINGO2	ENST00000698399.1	c.-35-61451A>G		intron_variant	Intron 6 of 6		NM_001258282.3	ENSP00000513694.1

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18381 AN: 152016 Hom.: 1221 Cov.: 32

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.0885

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.121 AC: 18409 AN: 152134 Hom.: 1225 Cov.: 32 AF XY: 0.122 AC XY: 9093 AN XY: 74356

African (AFR) AF: 0.117 AC: 4849 AN: 41518

American (AMR) AF: 0.0884 AC: 1350 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 452 AN: 3470

East Asian (EAS) AF: 0.120 AC: 620 AN: 5160

South Asian (SAS) AF: 0.220 AC: 1061 AN: 4818

European-Finnish (FIN) AF: 0.116 AC: 1229 AN: 10590

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.124 AC: 8439 AN: 67976

Other (OTH) AF: 0.121 AC: 257 AN: 2116

Alfa AF: 0.124 Hom.: 241

Bravo AF: 0.118

Asia WGS AF: 0.169 AC: 585 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	8.1
DANN	Benign	0.64
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs11793421; hg19: chr9-28012155;