rs11998784

Variant names:

• chr9-28875334-A-G
• rs11998784
• NM_001258282.3:c.-395+72484T>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.-395+72484T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 151,988 control chromosomes in the GnomAD database, including 2,027 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 0.14 (2027 hom., cov: 32)
• Consequence: LINGO2 NM_001258282.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0100
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LINGO2	NM_001258282.3	c.-395+72484T>C		intron_variant	Intron 2 of 6	ENST00000698399.1	NP_001245211.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LINGO2	ENST00000698399.1	c.-395+72484T>C		intron_variant	Intron 2 of 6		NM_001258282.3	ENSP00000513694.1
LINGO2	ENST00000698401.1	c.-765+72484T>C		intron_variant	Intron 2 of 7			ENSP00000513696.1
LINGO2	ENST00000698402.1	c.-550+72484T>C		intron_variant	Intron 2 of 7			ENSP00000513697.1
LINGO2	ENST00000698404.1	c.-506+72484T>C		intron_variant	Intron 2 of 8			ENSP00000513699.1

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20737 AN: 151870 Hom.: 2028 Cov.: 32

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0997

Gnomad ASJ AF: 0.0695

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.0954

Gnomad FIN AF: 0.0978

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.0774

Gnomad OTH AF: 0.118

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

GnomAD4 genome AF: 0.137 AC: 20754 AN: 151988 Hom.: 2027 Cov.: 32 AF XY: 0.136 AC XY: 10131 AN XY: 74314

African (AFR) AF: 0.275 AC: 11390 AN: 41424

American (AMR) AF: 0.0998 AC: 1519 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.0695 AC: 241 AN: 3466

East Asian (EAS) AF: 0.105 AC: 545 AN: 5180

South Asian (SAS) AF: 0.0955 AC: 461 AN: 4828

European-Finnish (FIN) AF: 0.0978 AC: 1036 AN: 10592

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.0774 AC: 5259 AN: 67966

Other (OTH) AF: 0.116 AC: 245 AN: 2112

Alfa AF: 0.121 Hom.: 278

Bravo AF: 0.142

Asia WGS AF: 0.107 AC: 371 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.0
DANN	Benign	0.31
PhyloP100		0.010

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11998784; hg19: chr9-28875332;