rs11793421

Positions:

• chr9-28012157-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.89).
• 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/exons	MANE	UniProt
LINGO2	NM_001258282.3	c.-35-61451A>G		intron_variant		ENST00000698399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LINGO2	ENST00000698399.1	c.-35-61451A>G		intron_variant			NM_001258282.3	P1

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

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.0884

Gnomad4 ASJ AF: 0.130

Gnomad4 EAS AF: 0.120

Gnomad4 SAS AF: 0.220

Gnomad4 FIN AF: 0.116

Gnomad4 NFE AF: 0.124

Gnomad4 OTH AF: 0.121

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs11793421; hg19: chr9-28012155;