rs944648

Variant names:

• chr9-28025179-C-G
• rs944648
• NM_001258282.3:c.-35-74473G>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.-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
• Publications: 1 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001258282.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINGO2	NM_001258282.3	MANE Select	c.-35-74473G>C		intron	N/A	NP_001245211.1
	LINGO2	NM_001354574.2		c.-35-74473G>C		intron	N/A	NP_001341503.1
	LINGO2	NM_001354575.2		c.-35-74473G>C		intron	N/A	NP_001341504.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINGO2	ENST00000698399.1	MANE Select	c.-35-74473G>C		intron	N/A	ENSP00000513694.1
	LINGO2	ENST00000379992.6	TSL:5	c.-86-12774G>C		intron	N/A	ENSP00000369328.1
	LINGO2	ENST00000698400.1		c.-36+1080G>C		intron	N/A	ENSP00000513695.1

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

African (AFR) AF: 0.451 AC: 18678 AN: 41446

American (AMR) AF: 0.748 AC: 11424 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.736 AC: 2553 AN: 3470

East Asian (EAS) AF: 0.467 AC: 2399 AN: 5140

South Asian (SAS) AF: 0.596 AC: 2875 AN: 4820

European-Finnish (FIN) AF: 0.630 AC: 6657 AN: 10560

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.695 AC: 47229 AN: 67980

Other (OTH) AF: 0.664 AC: 1404 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.51
PhyloP100		-0.38
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: rs944648; hg19: chr9-28025177;