rs944648

Positions:

• chr9-28025179-C-G

Variant summary

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

The NM_001258282.3(LINGO2):​c.-35-74473G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.62 in 152,000 control chromosomes in the GnomAD database, including 30,153 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 0.62 (30153 hom., cov: 32)
• Consequence: LINGO2 NM_001258282.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.377

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LINGO2	NM_001258282.3	c.-35-74473G>C		intron_variant		ENST00000698399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LINGO2	ENST00000698399.1	c.-35-74473G>C		intron_variant			NM_001258282.3	P1

Frequencies

GnomAD3 genomes AF: 0.620 AC: 94152 AN: 151882 Hom.: 30148 Cov.: 32

Gnomad AFR AF: 0.451

Gnomad AMI AF: 0.840

Gnomad AMR AF: 0.748

Gnomad ASJ AF: 0.736

Gnomad EAS AF: 0.467

Gnomad SAS AF: 0.597

Gnomad FIN AF: 0.630

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.695

Gnomad OTH AF: 0.667

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

GnomAD4 genome AF: 0.620 AC: 94192 AN: 152000 Hom.: 30153 Cov.: 32 AF XY: 0.619 AC XY: 45984 AN XY: 74250

Gnomad4 AFR AF: 0.451

Gnomad4 AMR AF: 0.748

Gnomad4 ASJ AF: 0.736

Gnomad4 EAS AF: 0.467

Gnomad4 SAS AF: 0.596

Gnomad4 FIN AF: 0.630

Gnomad4 NFE AF: 0.695

Gnomad4 OTH AF: 0.664

Alfa AF: 0.639 Hom.: 3948

Bravo AF: 0.622

Asia WGS AF: 0.542 AC: 1889 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.51

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: rs944648; hg19: chr9-28025177;