9-28374692-C-T

Position:

• chr9-28374692-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LINGO2	NM_001258282.3	c.-227-1824G>A		intron_variant		ENST00000698399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LINGO2	ENST00000698399.1	c.-227-1824G>A		intron_variant			NM_001258282.3	P1

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

Gnomad4 AFR AF: 0.317

Gnomad4 AMR AF: 0.554

Gnomad4 ASJ AF: 0.592

Gnomad4 EAS AF: 0.375

Gnomad4 SAS AF: 0.424

Gnomad4 FIN AF: 0.683

Gnomad4 NFE AF: 0.594

Gnomad4 OTH AF: 0.526

Alfa AF: 0.564 Hom.: 11060

Bravo AF: 0.496

Asia WGS AF: 0.389 AC: 1355 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.51
DANN	Benign	0.32

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

Publications

LitVar

Other links and lift over

dbSNP: rs16912778; hg19: chr9-28374690; COSMIC: COSV66143808;