9-28370763-C-T

Position:

• chr9-28370763-C-T

Variant summary

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

The NM_001258282.3(LINGO2):​c.-195+2073G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 152,184 control chromosomes in the GnomAD database, including 1,030 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 (1030 hom., cov: 32)
• Consequence: LINGO2 NM_001258282.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.67

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LINGO2	NM_001258282.3	c.-195+2073G>A		intron_variant		ENST00000698399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LINGO2	ENST00000698399.1	c.-195+2073G>A		intron_variant			NM_001258282.3	P1

Frequencies

GnomAD3 genomes AF: 0.112 AC: 17100 AN: 152066 Hom.: 1028 Cov.: 32

Gnomad AFR AF: 0.0848

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.0974

Gnomad EAS AF: 0.0990

Gnomad SAS AF: 0.0765

Gnomad FIN AF: 0.0886

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.113 AC: 17125 AN: 152184 Hom.: 1030 Cov.: 32 AF XY: 0.111 AC XY: 8263 AN XY: 74398

Gnomad4 AFR AF: 0.0852

Gnomad4 AMR AF: 0.163

Gnomad4 ASJ AF: 0.0974

Gnomad4 EAS AF: 0.0990

Gnomad4 SAS AF: 0.0768

Gnomad4 FIN AF: 0.0886

Gnomad4 NFE AF: 0.124

Gnomad4 OTH AF: 0.118

Alfa AF: 0.121 Hom.: 1100

Bravo AF: 0.117

Asia WGS AF: 0.105 AC: 368 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.043
DANN	Benign	0.60

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: rs16912763; hg19: chr9-28370761;