9-28372746-C-G

Variant names:

• chr9-28372746-C-G
• rs2383768
• NM_001258282.3:c.-195+90G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001258282.3(LINGO2):​c.-195+90G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.784 in 152,488 control chromosomes in the GnomAD database, including 48,106 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 0.78 (47934 hom., cov: 32)
  • Exomes 𝑓: 0.89 (172 hom.)
• Consequence: LINGO2 NM_001258282.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.03
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.856 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LINGO2	NM_001258282.3	c.-195+90G>C		intron_variant	Intron 5 of 6	ENST00000698399.1	NP_001245211.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LINGO2	ENST00000698399.1	c.-195+90G>C		intron_variant	Intron 5 of 6		NM_001258282.3	ENSP00000513694.1

Frequencies

GnomAD3 genomes AF: 0.784 AC: 119079 AN: 151938 Hom.: 47889 Cov.: 32

Gnomad AFR AF: 0.589

Gnomad AMI AF: 0.945

Gnomad AMR AF: 0.853

Gnomad ASJ AF: 0.832

Gnomad EAS AF: 0.750

Gnomad SAS AF: 0.875

Gnomad FIN AF: 0.874

Gnomad MID AF: 0.886

Gnomad NFE AF: 0.862

Gnomad OTH AF: 0.825

GnomAD4 exome AF: 0.894 AC: 386 AN: 432 Hom.: 172 AF XY: 0.885 AC XY: 230 AN XY: 260

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.892 AC: 380 AN: 426

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 2 AN: 2

Other (OTH) AF: 1.00 AC: 4 AN: 4

GnomAD4 genome AF: 0.784 AC: 119182 AN: 152056 Hom.: 47934 Cov.: 32 AF XY: 0.785 AC XY: 58382 AN XY: 74330

African (AFR) AF: 0.590 AC: 24449 AN: 41466

American (AMR) AF: 0.853 AC: 13036 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.832 AC: 2879 AN: 3462

East Asian (EAS) AF: 0.750 AC: 3877 AN: 5166

South Asian (SAS) AF: 0.876 AC: 4218 AN: 4816

European-Finnish (FIN) AF: 0.874 AC: 9259 AN: 10588

Middle Eastern (MID) AF: 0.901 AC: 265 AN: 294

European-Non Finnish (NFE) AF: 0.862 AC: 58596 AN: 67966

Other (OTH) AF: 0.826 AC: 1741 AN: 2108

Alfa AF: 0.818 Hom.: 6077

Bravo AF: 0.777

Asia WGS AF: 0.822 AC: 2841 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.34
DANN	Benign	0.39
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2383768; hg19: chr9-28372744;