9-28001946-A-G

Variant names:

• chr9-28001946-A-G
• rs1197944
• NM_001258282.3:c.-35-51240T>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.-35-51240T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 152,104 control chromosomes in the GnomAD database, including 25,187 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 0.57 (25187 hom., cov: 33)
• Consequence: LINGO2 NM_001258282.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.578
• Publications: 1 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.819 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LINGO2	NM_001258282.3	c.-35-51240T>C		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.-35-51240T>C		intron_variant	Intron 6 of 6		NM_001258282.3	ENSP00000513694.1

Frequencies

GnomAD3 genomes AF: 0.568 AC: 86370 AN: 151986 Hom.: 25155 Cov.: 33

Gnomad AFR AF: 0.655

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.601

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.840

Gnomad SAS AF: 0.489

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.516

Gnomad OTH AF: 0.560

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

GnomAD4 genome AF: 0.568 AC: 86443 AN: 152104 Hom.: 25187 Cov.: 33 AF XY: 0.569 AC XY: 42332 AN XY: 74340

African (AFR) AF: 0.655 AC: 27159 AN: 41484

American (AMR) AF: 0.601 AC: 9192 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 1638 AN: 3466

East Asian (EAS) AF: 0.839 AC: 4338 AN: 5168

South Asian (SAS) AF: 0.490 AC: 2361 AN: 4818

European-Finnish (FIN) AF: 0.468 AC: 4941 AN: 10564

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.516 AC: 35100 AN: 68002

Other (OTH) AF: 0.555 AC: 1172 AN: 2112

Alfa AF: 0.529 Hom.: 61524

Bravo AF: 0.585

Asia WGS AF: 0.650 AC: 2256 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.70
DANN	Benign	0.51
PhyloP100		-0.58
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: rs1197944; hg19: chr9-28001944;