9-28374692-C-T

Variant names:

• chr9-28374692-C-T
• rs16912778
• NM_001258282.3:c.-227-1824G>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.-227-1824G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 151,922 control chromosomes in the GnomAD database, including 20,962 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 0.51 (20962 hom., cov: 31)
• Consequence: LINGO2 NM_001258282.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.228
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.589 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.-227-1824G>A		intron	N/A	NP_001245211.1	Q7L985
	LINGO2	NM_001354574.2		c.-194-79326G>A		intron	N/A	NP_001341503.1	Q7L985
	LINGO2	NM_001354575.2		c.-227-1824G>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.-227-1824G>A		intron	N/A	ENSP00000513694.1	Q7L985
	LINGO2	ENST00000379992.6	TSL:5	c.-278-1824G>A		intron	N/A	ENSP00000369328.1	Q7L985
	LINGO2	ENST00000698400.1		c.-442-1824G>A		intron	N/A	ENSP00000513695.1	Q7L985

Frequencies

GnomAD3 genomes AF: 0.507 AC: 77027 AN: 151804 Hom.: 20950 Cov.: 31

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.743

Gnomad AMR AF: 0.555

Gnomad ASJ AF: 0.592

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.683

Gnomad MID AF: 0.458

Gnomad NFE AF: 0.594

Gnomad OTH AF: 0.531

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

GnomAD4 genome AF: 0.507 AC: 77077 AN: 151922 Hom.: 20962 Cov.: 31 AF XY: 0.509 AC XY: 37814 AN XY: 74248

African (AFR) AF: 0.317 AC: 13124 AN: 41426

American (AMR) AF: 0.554 AC: 8459 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.592 AC: 2053 AN: 3466

East Asian (EAS) AF: 0.375 AC: 1923 AN: 5128

South Asian (SAS) AF: 0.424 AC: 2040 AN: 4806

European-Finnish (FIN) AF: 0.683 AC: 7210 AN: 10560

Middle Eastern (MID) AF: 0.462 AC: 133 AN: 288

European-Non Finnish (NFE) AF: 0.594 AC: 40350 AN: 67968

Other (OTH) AF: 0.526 AC: 1110 AN: 2112

Alfa AF: 0.563 Hom.: 12439

Bravo AF: 0.496

Asia WGS AF: 0.389 AC: 1355 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.51
DANN	Benign	0.32
PhyloP100		-0.23
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: rs16912778; hg19: chr9-28374690; COSMIC: COSV66143808;