rs994367

Variant names:

• chr9-28087581-T-A
• rs994367
• NM_001258282.3:c.-35-136875A>T

Your query was ambiguous. Multiple possible variants found:

• chr9-28087581-T-A
• chr9-28087581-T-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001258282.3(LINGO2):​c.-35-136875A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 151,684 control chromosomes in the GnomAD database, including 14,770 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 0.44 (14770 hom., cov: 31)
• Consequence: LINGO2 NM_001258282.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.281
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.66 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LINGO2	NM_001258282.3	c.-35-136875A>T		intron_variant	Intron 6 of 6	ENST00000698399.1	NP_001245211.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LINGO2	ENST00000698399.1	c.-35-136875A>T		intron_variant	Intron 6 of 6		NM_001258282.3	ENSP00000513694.1

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66392 AN: 151564 Hom.: 14772 Cov.: 31

Gnomad AFR AF: 0.390

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.679

Gnomad SAS AF: 0.500

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.439

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

GnomAD4 genome AF: 0.438 AC: 66415 AN: 151684 Hom.: 14770 Cov.: 31 AF XY: 0.438 AC XY: 32486 AN XY: 74106

African (AFR) AF: 0.390 AC: 16123 AN: 41354

American (AMR) AF: 0.450 AC: 6837 AN: 15188

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 1639 AN: 3462

East Asian (EAS) AF: 0.679 AC: 3481 AN: 5128

South Asian (SAS) AF: 0.499 AC: 2403 AN: 4814

European-Finnish (FIN) AF: 0.415 AC: 4377 AN: 10552

Middle Eastern (MID) AF: 0.387 AC: 113 AN: 292

European-Non Finnish (NFE) AF: 0.447 AC: 30330 AN: 67874

Other (OTH) AF: 0.436 AC: 920 AN: 2110

Alfa AF: 0.297 Hom.: 758

Bravo AF: 0.437

Asia WGS AF: 0.553 AC: 1919 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.2
DANN	Benign	0.80
PhyloP100		0.28
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: rs994367; hg19: chr9-28087579;