9-28659145-A-G

Position:

• chr9-28659145-A-G

Variant summary

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

The NM_001258282.3(LINGO2):​c.-314+11055T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 152,058 control chromosomes in the GnomAD database, including 3,987 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 0.18 (3987 hom., cov: 32)
• Consequence: LINGO2 NM_001258282.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0930

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LINGO2	NM_001258282.3	c.-314+11055T>C		intron_variant		ENST00000698399.1	NP_001245211.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LINGO2	ENST00000698399.1	c.-314+11055T>C		intron_variant			NM_001258282.3	ENSP00000513694	P1

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27548 AN: 151942 Hom.: 3955 Cov.: 32

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.0357

Gnomad SAS AF: 0.0732

Gnomad FIN AF: 0.0934

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.0947

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.182 AC: 27637 AN: 152058 Hom.: 3987 Cov.: 32 AF XY: 0.179 AC XY: 13272 AN XY: 74332

Gnomad4 AFR AF: 0.403

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.0354

Gnomad4 SAS AF: 0.0733

Gnomad4 FIN AF: 0.0934

Gnomad4 NFE AF: 0.0947

Gnomad4 OTH AF: 0.176

Alfa AF: 0.110 Hom.: 1641

Bravo AF: 0.194

Asia WGS AF: 0.0910 AC: 315 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.9
DANN	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs7046685; hg19: chr9-28659143;