9-28478307-A-T

Position:

• chr9-28478307-A-T

Variant summary

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

The NM_001258282.3(LINGO2):​c.-313-2282T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 151,946 control chromosomes in the GnomAD database, including 18,986 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 0.48 (18986 hom., cov: 32)
• Consequence: LINGO2 NM_001258282.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.82

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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LINGO2	NM_001258282.3	c.-313-2282T>A		intron_variant		ENST00000698399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LINGO2	ENST00000698399.1	c.-313-2282T>A		intron_variant			NM_001258282.3	P1

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72602 AN: 151828 Hom.: 18978 Cov.: 32

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.815

Gnomad AMR AF: 0.555

Gnomad ASJ AF: 0.590

Gnomad EAS AF: 0.428

Gnomad SAS AF: 0.529

Gnomad FIN AF: 0.549

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.570

Gnomad OTH AF: 0.518

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

GnomAD4 genome AF: 0.478 AC: 72642 AN: 151946 Hom.: 18986 Cov.: 32 AF XY: 0.481 AC XY: 35757 AN XY: 74282

Gnomad4 AFR AF: 0.261

Gnomad4 AMR AF: 0.555

Gnomad4 ASJ AF: 0.590

Gnomad4 EAS AF: 0.429

Gnomad4 SAS AF: 0.527

Gnomad4 FIN AF: 0.549

Gnomad4 NFE AF: 0.570

Gnomad4 OTH AF: 0.520

Alfa AF: 0.501 Hom.: 2505

Bravo AF: 0.468

Asia WGS AF: 0.496 AC: 1723 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.8
DANN	Benign	0.58

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: rs1412229; hg19: chr9-28478305;