9-28477084-G-T

Variant names:

• chr9-28477084-G-T
• rs10757744
• NM_001258282.3:c.-313-1059C>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.-313-1059C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.861 in 152,158 control chromosomes in the GnomAD database, including 56,680 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 0.86 (56680 hom., cov: 31)
• Consequence: LINGO2 NM_001258282.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.297
• Publications: 3 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=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001258282.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINGO2	NM_001258282.3	MANE Select	c.-313-1059C>A		intron	N/A	NP_001245211.1	Q7L985
	LINGO2	NM_001354574.2		c.-280-1059C>A		intron	N/A	NP_001341503.1	Q7L985
	LINGO2	NM_001354575.2		c.-313-1059C>A		intron	N/A	NP_001341504.1	Q7L985

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINGO2	ENST00000698399.1	MANE Select	c.-313-1059C>A		intron	N/A	ENSP00000513694.1	Q7L985
	LINGO2	ENST00000379992.6	TSL:5	c.-364-1059C>A		intron	N/A	ENSP00000369328.1	Q7L985
	LINGO2	ENST00000698400.1		c.-528-1059C>A		intron	N/A	ENSP00000513695.1	Q7L985

Frequencies

GnomAD3 genomes AF: 0.861 AC: 130956 AN: 152040 Hom.: 56629 Cov.: 31

Gnomad AFR AF: 0.793

Gnomad AMI AF: 0.746

Gnomad AMR AF: 0.886

Gnomad ASJ AF: 0.835

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.963

Gnomad FIN AF: 0.929

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.873

Gnomad OTH AF: 0.837

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

GnomAD4 genome AF: 0.861 AC: 131064 AN: 152158 Hom.: 56680 Cov.: 31 AF XY: 0.867 AC XY: 64484 AN XY: 74396

African (AFR) AF: 0.793 AC: 32895 AN: 41488

American (AMR) AF: 0.886 AC: 13539 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.835 AC: 2898 AN: 3470

East Asian (EAS) AF: 0.999 AC: 5169 AN: 5172

South Asian (SAS) AF: 0.963 AC: 4653 AN: 4832

European-Finnish (FIN) AF: 0.929 AC: 9854 AN: 10608

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.873 AC: 59379 AN: 67996

Other (OTH) AF: 0.838 AC: 1764 AN: 2106

Alfa AF: 0.861 Hom.: 59033

Bravo AF: 0.853

Asia WGS AF: 0.970 AC: 3372 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.33
DANN	Benign	0.34
PhyloP100		-0.30
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: rs10757744; hg19: chr9-28477082;