chr9-28294233-T-C

Position:

• chr9-28294233-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001258282.3(LINGO2):​c.-36+975A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 151,954 control chromosomes in the GnomAD database, including 18,697 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 0.49 (18697 hom., cov: 32)
• Consequence: LINGO2 NM_001258282.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.284

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LINGO2	NM_001258282.3	c.-36+975A>G		intron_variant		ENST00000698399.1	NP_001245211.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LINGO2	ENST00000698399.1	c.-36+975A>G		intron_variant			NM_001258282.3	ENSP00000513694	P1

Frequencies

GnomAD3 genomes AF: 0.493 AC: 74900 AN: 151836 Hom.: 18686 Cov.: 32

Gnomad AFR AF: 0.444

Gnomad AMI AF: 0.503

Gnomad AMR AF: 0.459

Gnomad ASJ AF: 0.550

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.530

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.514

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

GnomAD4 genome AF: 0.493 AC: 74938 AN: 151954 Hom.: 18697 Cov.: 32 AF XY: 0.487 AC XY: 36160 AN XY: 74260

Gnomad4 AFR AF: 0.445

Gnomad4 AMR AF: 0.459

Gnomad4 ASJ AF: 0.550

Gnomad4 EAS AF: 0.473

Gnomad4 SAS AF: 0.530

Gnomad4 FIN AF: 0.460

Gnomad4 NFE AF: 0.531

Gnomad4 OTH AF: 0.509

Alfa AF: 0.523 Hom.: 26544

Bravo AF: 0.491

Asia WGS AF: 0.450 AC: 1562 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.7
DANN	Benign	0.50

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: rs10812774; hg19: chr9-28294231;