rs11998784

chr9-28875334-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.9).
• 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/exons	MANE	UniProt
LINGO2	NM_001258282.3	c.-395+72484T>C		intron_variant		ENST00000698399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LINGO2	ENST00000698399.1	c.-395+72484T>C		intron_variant			NM_001258282.3	P1
LINGO2	ENST00000698401.1	c.-765+72484T>C		intron_variant				P1
LINGO2	ENST00000698402.1	c.-550+72484T>C		intron_variant				P1
LINGO2	ENST00000698404.1	c.-506+72484T>C		intron_variant

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

Gnomad4 AFR AF: 0.275

Gnomad4 AMR AF: 0.0998

Gnomad4 ASJ AF: 0.0695

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.0955

Gnomad4 FIN AF: 0.0978

Gnomad4 NFE AF: 0.0774

Gnomad4 OTH AF: 0.116

Alfa AF: 0.116 Hom.: 249

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11998784; hg19: chr9-28875332;