chr9-28879955-C-A

Position:

• chr9-28879955-C-A

Variant summary

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

The NM_001258282.3(LINGO2):​c.-395+67863G>T 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 152,070 control chromosomes in the GnomAD database, including 2,031 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 (2031 hom., cov: 33)
• Consequence: LINGO2 NM_001258282.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.267

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=-0.88).
• 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	Protein	UniProt
LINGO2	NM_001258282.3	c.-395+67863G>T		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+67863G>T		intron_variant			NM_001258282.3	ENSP00000513694	P1
LINGO2	ENST00000698401.1	c.-765+67863G>T		intron_variant				ENSP00000513696	P1
LINGO2	ENST00000698402.1	c.-550+67863G>T		intron_variant				ENSP00000513697	P1
LINGO2	ENST00000698404.1	c.-506+67863G>T		intron_variant				ENSP00000513699

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20772 AN: 151954 Hom.: 2032 Cov.: 33

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0996

Gnomad ASJ AF: 0.0695

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.0992

Gnomad FIN AF: 0.0975

Gnomad MID AF: 0.156

Gnomad NFE AF: 0.0773

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: 20786 AN: 152070 Hom.: 2031 Cov.: 33 AF XY: 0.136 AC XY: 10136 AN XY: 74334

Gnomad4 AFR AF: 0.275

Gnomad4 AMR AF: 0.0996

Gnomad4 ASJ AF: 0.0695

Gnomad4 EAS AF: 0.106

Gnomad4 SAS AF: 0.0993

Gnomad4 FIN AF: 0.0975

Gnomad4 NFE AF: 0.0773

Gnomad4 OTH AF: 0.116

Alfa AF: 0.0782 Hom.: 261

Bravo AF: 0.142

Asia WGS AF: 0.109 AC: 378 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.32

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1368998; hg19: chr9-28879953;