rs13299777

Positions:

• chr9-28939556-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.-395+8262A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,226 control chromosomes in the GnomAD database, including 986 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 (986 hom., cov: 32)
• Consequence: LINGO2 NM_001258282.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25

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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LINGO2	NM_001258282.3	c.-395+8262A>G		intron_variant		ENST00000698399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LINGO2	ENST00000698399.1	c.-395+8262A>G		intron_variant			NM_001258282.3	P1
LINGO2	ENST00000698401.1	c.-765+8262A>G		intron_variant				P1
LINGO2	ENST00000698402.1	c.-550+8262A>G		intron_variant				P1
LINGO2	ENST00000698404.1	c.-506+8262A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17311 AN: 152108 Hom.: 988 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.0614

Gnomad AMR AF: 0.0909

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.114 AC: 17318 AN: 152226 Hom.: 986 Cov.: 32 AF XY: 0.115 AC XY: 8527 AN XY: 74422

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.0908

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.120

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.106

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.115

Alfa AF: 0.118 Hom.: 182

Bravo AF: 0.111

Asia WGS AF: 0.134 AC: 464 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.030
DANN	Benign	0.51

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs13299777; hg19: chr9-28939554;