rs1389728

Positions:

• chr9-28817959-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+129859A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0989 in 152,194 control chromosomes in the GnomAD database, including 814 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 0.099 (814 hom., cov: 32)
• Consequence: LINGO2 NM_001258282.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.306

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LINGO2	NM_001258282.3	c.-395+129859A>G		intron_variant		ENST00000698399.1	NP_001245211.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LINGO2	ENST00000698399.1	c.-395+129859A>G		intron_variant			NM_001258282.3	ENSP00000513694	P1
LINGO2	ENST00000698401.1	c.-765+129859A>G		intron_variant				ENSP00000513696	P1
LINGO2	ENST00000698402.1	c.-550+129859A>G		intron_variant				ENSP00000513697	P1
LINGO2	ENST00000698404.1	c.-506+129859A>G		intron_variant				ENSP00000513699

Frequencies

GnomAD3 genomes AF: 0.0989 AC: 15042 AN: 152076 Hom.: 815 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0843

Gnomad ASJ AF: 0.0660

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.0894

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0848

Gnomad OTH AF: 0.0869

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

GnomAD4 genome AF: 0.0989 AC: 15052 AN: 152194 Hom.: 814 Cov.: 32 AF XY: 0.101 AC XY: 7538 AN XY: 74428

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.0845

Gnomad4 ASJ AF: 0.0660

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.0893

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.0848

Gnomad4 OTH AF: 0.0859

Alfa AF: 0.0846 Hom.: 997

Bravo AF: 0.0950

Asia WGS AF: 0.0930 AC: 323 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.6
DANN	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1389728; hg19: chr9-28817957;