rs16912763

Variant names:

• chr9-28370763-C-T
• rs16912763
• NM_001258282.3:c.-195+2073G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
LINGO2	NM_001258282.3	c.-195+2073G>A		intron_variant	Intron 5 of 6	ENST00000698399.1	NP_001245211.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LINGO2	ENST00000698399.1	c.-195+2073G>A		intron_variant	Intron 5 of 6		NM_001258282.3	ENSP00000513694.1

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

African (AFR) AF: 0.0852 AC: 3538 AN: 41528

American (AMR) AF: 0.163 AC: 2495 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0974 AC: 338 AN: 3472

East Asian (EAS) AF: 0.0990 AC: 512 AN: 5170

South Asian (SAS) AF: 0.0768 AC: 370 AN: 4818

European-Finnish (FIN) AF: 0.0886 AC: 938 AN: 10586

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.124 AC: 8403 AN: 68000

Other (OTH) AF: 0.118 AC: 249 AN: 2116

Alfa AF: 0.118 Hom.: 1708

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
PhyloP100		-3.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs16912763; hg19: chr9-28370761;