Genetic Variant LINGO2:c.-195+90G>C (chr9-28372746-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.03

Publications

2 publications found

Variant links:

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]

LINGO2 links:

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ACMG classification

Classification was made for transcript

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.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LINGO2	NM_001258282.3	MANE Select	c.-195+90G>C	intron	N/A	NP_001245211.1	Q7L985
LINGO2	NM_001354574.2		c.-194-77380G>C	intron	N/A	NP_001341503.1	Q7L985
LINGO2	NM_001354575.2		c.-195+90G>C	intron	N/A	NP_001341504.1	Q7L985

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LINGO2	ENST00000698399.1	MANE Select	c.-195+90G>C	intron	N/A	ENSP00000513694.1	Q7L985
LINGO2	ENST00000379992.6	TSL:5	c.-246+90G>C	intron	N/A	ENSP00000369328.1	Q7L985
LINGO2	ENST00000698400.1		c.-410+90G>C	intron	N/A	ENSP00000513695.1	Q7L985

Frequencies

GnomAD3 genomes

AF:

0.784

AC:

119079

AN:

151938

Hom.:

47889

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.892

AC:

380

AN:

426

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

1.00

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.784

AC:

119182

AN:

152056

Hom.:

47934

Cov.:

AF XY:

0.785

AC XY:

58382

AN XY:

74330

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1251

2502

3753

5004

6255

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

860

1720

2580

3440

4300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.34

(source)

DANN

Benign

0.39

PhyloP100

-2.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over