rs13440446

Positions:

• chr9-28251543-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+43665A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 152,002 control chromosomes in the GnomAD database, including 3,780 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 0.21 (3780 hom., cov: 32)
• Consequence: LINGO2 NM_001258282.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18

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 (EAS) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LINGO2	NM_001258282.3	c.-36+43665A>G		intron_variant		ENST00000698399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LINGO2	ENST00000698399.1	c.-36+43665A>G		intron_variant			NM_001258282.3	P1

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32511 AN: 151884 Hom.: 3778 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.0824

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.208

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

GnomAD4 genome AF: 0.214 AC: 32528 AN: 152002 Hom.: 3780 Cov.: 32 AF XY: 0.216 AC XY: 16048 AN XY: 74302

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.206

Gnomad4 ASJ AF: 0.181

Gnomad4 EAS AF: 0.268

Gnomad4 SAS AF: 0.200

Gnomad4 FIN AF: 0.300

Gnomad4 NFE AF: 0.253

Gnomad4 OTH AF: 0.211

Alfa AF: 0.241 Hom.: 803

Bravo AF: 0.205

Asia WGS AF: 0.236 AC: 821 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.98
DANN	Benign	0.56

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: rs13440446; hg19: chr9-28251541;