9-28374102-C-T

Position:

• chr9-28374102-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.-227-1234G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 151,260 control chromosomes in the GnomAD database, including 10,288 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 0.34 (10288 hom., cov: 29)
• Consequence: LINGO2 NM_001258282.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.629

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LINGO2	NM_001258282.3	c.-227-1234G>A		intron_variant		ENST00000698399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LINGO2	ENST00000698399.1	c.-227-1234G>A		intron_variant			NM_001258282.3	P1

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52044 AN: 151158 Hom.: 10291 Cov.: 29

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.318

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.321

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.355

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

GnomAD4 genome AF: 0.344 AC: 52042 AN: 151260 Hom.: 10288 Cov.: 29 AF XY: 0.350 AC XY: 25832 AN XY: 73838

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.351

Gnomad4 ASJ AF: 0.445

Gnomad4 EAS AF: 0.274

Gnomad4 SAS AF: 0.336

Gnomad4 FIN AF: 0.570

Gnomad4 NFE AF: 0.424

Gnomad4 OTH AF: 0.351

Alfa AF: 0.402 Hom.: 2983

Bravo AF: 0.324

Asia WGS AF: 0.269 AC: 936 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.90

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: rs10968542; hg19: chr9-28374100; COSMIC: COSV66143801;