rs1438478

Positions:

• chr9-28719215-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001258282.3(LINGO2):​c.-394-48935A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,060 control chromosomes in the GnomAD database, including 1,027 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 0.11 (1027 hom., cov: 32)
• Consequence: LINGO2 NM_001258282.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0630

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LINGO2	NM_001258282.3	c.-394-48935A>C		intron_variant		ENST00000698399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LINGO2	ENST00000698399.1	c.-394-48935A>C		intron_variant			NM_001258282.3	P1
LINGO2	ENST00000698401.1	c.-764-48935A>C		intron_variant				P1
LINGO2	ENST00000698402.1	c.-549-48935A>C		intron_variant				P1
LINGO2	ENST00000698404.1	c.-505-48935A>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16088 AN: 151942 Hom.: 1027 Cov.: 32

Gnomad AFR AF: 0.0595

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0983

Gnomad ASJ AF: 0.0421

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.0996

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

GnomAD4 genome AF: 0.106 AC: 16084 AN: 152060 Hom.: 1027 Cov.: 32 AF XY: 0.111 AC XY: 8243 AN XY: 74326

Gnomad4 AFR AF: 0.0593

Gnomad4 AMR AF: 0.0980

Gnomad4 ASJ AF: 0.0421

Gnomad4 EAS AF: 0.192

Gnomad4 SAS AF: 0.142

Gnomad4 FIN AF: 0.192

Gnomad4 NFE AF: 0.118

Gnomad4 OTH AF: 0.0986

Alfa AF: 0.110 Hom.: 1406

Bravo AF: 0.0953

Asia WGS AF: 0.146 AC: 509 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.99
DANN	Benign	0.33

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1438478; hg19: chr9-28719213;