chr9-28010244-A-T

Variant names:

• chr9-28010244-A-T
• rs7854367
• NM_001258282.3:c.-35-59538T>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.-35-59538T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 152,106 control chromosomes in the GnomAD database, including 5,210 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 0.26 (5210 hom., cov: 32)
• Consequence: LINGO2 NM_001258282.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.328 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.-35-59538T>A		intron	N/A	NP_001245211.1	Q7L985
	LINGO2	NM_001354574.2		c.-35-59538T>A		intron	N/A	NP_001341503.1	Q7L985
	LINGO2	NM_001354575.2		c.-35-59538T>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.-35-59538T>A		intron	N/A	ENSP00000513694.1	Q7L985
	LINGO2	ENST00000379992.6	TSL:5	c.-36+2111T>A		intron	N/A	ENSP00000369328.1	Q7L985
	LINGO2	ENST00000698400.1		c.-36+16015T>A		intron	N/A	ENSP00000513695.1	Q7L985

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38764 AN: 151988 Hom.: 5199 Cov.: 32

Gnomad AFR AF: 0.332

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.246

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

GnomAD4 genome AF: 0.255 AC: 38805 AN: 152106 Hom.: 5210 Cov.: 32 AF XY: 0.252 AC XY: 18765 AN XY: 74374

African (AFR) AF: 0.332 AC: 13784 AN: 41468

American (AMR) AF: 0.181 AC: 2773 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 866 AN: 3466

East Asian (EAS) AF: 0.175 AC: 907 AN: 5172

South Asian (SAS) AF: 0.287 AC: 1384 AN: 4818

European-Finnish (FIN) AF: 0.224 AC: 2371 AN: 10596

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.235 AC: 15982 AN: 67976

Other (OTH) AF: 0.247 AC: 522 AN: 2114

Alfa AF: 0.252 Hom.: 620

Bravo AF: 0.255

Asia WGS AF: 0.230 AC: 798 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.20
DANN	Benign	0.33
PhyloP100		-1.2
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: rs7854367; hg19: chr9-28010242;