9-28719761-G-T

Variant names:

• chr9-28719761-G-T
• rs6476092
• NM_001258282.3:c.-394-49481C>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001258282.3(LINGO2):​c.-394-49481C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000297 in 151,664 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00030 (0 hom., cov: 32)
• Consequence: LINGO2 NM_001258282.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0580
• Publications: 6 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS2: High AC in GnomAd4 at 45 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LINGO2	NM_001258282.3	c.-394-49481C>A		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.-394-49481C>A		intron_variant	Intron 2 of 6		NM_001258282.3	ENSP00000513694.1
LINGO2	ENST00000698401.1	c.-764-49481C>A		intron_variant	Intron 2 of 7			ENSP00000513696.1
LINGO2	ENST00000698402.1	c.-549-49481C>A		intron_variant	Intron 2 of 7			ENSP00000513697.1
LINGO2	ENST00000698404.1	c.-505-49481C>A		intron_variant	Intron 2 of 8			ENSP00000513699.1

Frequencies

GnomAD3 genomes AF: 0.000297 AC: 45 AN: 151664 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000726

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000589

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.000297 AC: 45 AN: 151664 Hom.: 0 Cov.: 32 AF XY: 0.000297 AC XY: 22 AN XY: 74012

African (AFR) AF: 0.0000726 AC: 3 AN: 41294

American (AMR) AF: 0.00 AC: 0 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 2 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10520

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000589 AC: 40 AN: 67896

Other (OTH) AF: 0.00 AC: 0 AN: 2078

Alfa AF: 0.000214 Hom.: 277

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.9
DANN	Benign	0.70
PhyloP100		-0.058

Splicing

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

Other links and lift over

dbSNP: rs6476092; hg19: chr9-28719759;