9-28509553-T-G

Position:

• chr9-28509553-T-G

Variant summary

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

The NM_001258282.3(LINGO2):​c.-313-33528A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.965 in 152,288 control chromosomes in the GnomAD database, including 71,039 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 0.96 (71039 hom., cov: 33)
• Consequence: LINGO2 NM_001258282.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.147

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.991 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LINGO2	NM_001258282.3	c.-313-33528A>C		intron_variant		ENST00000698399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LINGO2	ENST00000698399.1	c.-313-33528A>C		intron_variant			NM_001258282.3	P1

Frequencies

GnomAD3 genomes AF: 0.965 AC: 146848 AN: 152170 Hom.: 71011 Cov.: 33

Gnomad AFR AF: 0.910

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.986

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 0.879

Gnomad SAS AF: 0.945

Gnomad FIN AF: 0.977

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.997

Gnomad OTH AF: 0.973

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

GnomAD4 genome AF: 0.965 AC: 146928 AN: 152288 Hom.: 71039 Cov.: 33 AF XY: 0.963 AC XY: 71699 AN XY: 74442

Gnomad4 AFR AF: 0.910

Gnomad4 AMR AF: 0.986

Gnomad4 ASJ AF: 1.00

Gnomad4 EAS AF: 0.878

Gnomad4 SAS AF: 0.945

Gnomad4 FIN AF: 0.977

Gnomad4 NFE AF: 0.997

Gnomad4 OTH AF: 0.972

Alfa AF: 0.977 Hom.: 3579

Bravo AF: 0.963

Asia WGS AF: 0.920 AC: 3200 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.1
DANN	Benign	0.55

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: rs6476077; hg19: chr9-28509551;