9-28853127-C-T

Variant names:

• chr9-28853127-C-T
• rs16913751
• NM_001258282.3:c.-395+94691G>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.-395+94691G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 152,062 control chromosomes in the GnomAD database, including 2,526 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 0.15 (2526 hom., cov: 32)
• Consequence: LINGO2 NM_001258282.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0520
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.316 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINGO2	NM_001258282.3	MANE Select	c.-395+94691G>A		intron	N/A	NP_001245211.1
	LINGO2	NM_001354574.2		c.-362+94691G>A		intron	N/A	NP_001341503.1
	LINGO2	NM_001354575.2		c.-395+94691G>A		intron	N/A	NP_001341504.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINGO2	ENST00000698399.1	MANE Select	c.-395+94691G>A		intron	N/A	ENSP00000513694.1
	LINGO2	ENST00000698401.1		c.-765+94691G>A		intron	N/A	ENSP00000513696.1
	LINGO2	ENST00000698402.1		c.-550+94691G>A		intron	N/A	ENSP00000513697.1

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22580 AN: 151944 Hom.: 2520 Cov.: 32

Gnomad AFR AF: 0.321

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.0617

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.0891

Gnomad FIN AF: 0.0982

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.0768

Gnomad OTH AF: 0.120

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

GnomAD4 genome AF: 0.149 AC: 22626 AN: 152062 Hom.: 2526 Cov.: 32 AF XY: 0.147 AC XY: 10940 AN XY: 74334

African (AFR) AF: 0.321 AC: 13304 AN: 41454

American (AMR) AF: 0.102 AC: 1560 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.0617 AC: 214 AN: 3470

East Asian (EAS) AF: 0.107 AC: 547 AN: 5136

South Asian (SAS) AF: 0.0892 AC: 430 AN: 4822

European-Finnish (FIN) AF: 0.0982 AC: 1043 AN: 10624

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.0768 AC: 5223 AN: 67978

Other (OTH) AF: 0.119 AC: 252 AN: 2114

Alfa AF: 0.0992 Hom.: 1354

Bravo AF: 0.156

Asia WGS AF: 0.109 AC: 378 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.5
DANN	Benign	0.60
PhyloP100		0.052

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs16913751; hg19: chr9-28853125;