chr9-27950496-G-A
Position:
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP3BP4_ModerateBS2
The NM_001258282.3(LINGO2):c.176C>T(p.Thr59Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000105 in 1,596,730 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000098 ( 2 hom. )
Consequence
LINGO2
NM_001258282.3 missense
NM_001258282.3 missense
Scores
10
4
4
Clinical Significance
Conservation
PhyloP100: 9.96
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PP3
Multiple lines of computational evidence support a deleterious effect 10: AlphaMissense, BayesDel_addAF, BayesDel_noAF, Cadd, Dann, Eigen, phyloP100way_vertebrate, PrimateAI, PROVEAN, REVEL [when max_spliceai, FATHMM_MKL, MetaRNN, MutationAssessor, MutationTaster was below the threshold]
BP4
Computational evidence support a benign effect (MetaRNN=0.17575464).
BS2
High AC in GnomAd4 at 25 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LINGO2 | NM_001258282.3 | c.176C>T | p.Thr59Ile | missense_variant | 7/7 | ENST00000698399.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LINGO2 | ENST00000698399.1 | c.176C>T | p.Thr59Ile | missense_variant | 7/7 | NM_001258282.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000164 AC: 25AN: 152162Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
25
AN:
152162
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000184 AC: 44AN: 239378Hom.: 1 AF XY: 0.000218 AC XY: 28AN XY: 128658
GnomAD3 exomes
AF:
AC:
44
AN:
239378
Hom.:
AF XY:
AC XY:
28
AN XY:
128658
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000983 AC: 142AN: 1444568Hom.: 2 Cov.: 32 AF XY: 0.000112 AC XY: 80AN XY: 716156
GnomAD4 exome
AF:
AC:
142
AN:
1444568
Hom.:
Cov.:
32
AF XY:
AC XY:
80
AN XY:
716156
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.000164 AC: 25AN: 152162Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11AN XY: 74326
GnomAD4 genome
AF:
AC:
25
AN:
152162
Hom.:
Cov.:
32
AF XY:
AC XY:
11
AN XY:
74326
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
TwinsUK
AF:
AC:
0
ALSPAC
AF:
AC:
1
ESP6500AA
AF:
AC:
0
ESP6500EA
AF:
AC:
1
ExAC
AF:
AC:
10
Asia WGS
AF:
AC:
1
AN:
3476
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 29, 2023 | The c.176C>T (p.T59I) alteration is located in exon 7 (coding exon 1) of the LINGO2 gene. This alteration results from a C to T substitution at nucleotide position 176, causing the threonine (T) at amino acid position 59 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T
MetaSVM
Uncertain
T
MutationAssessor
Benign
N;N;N
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;.
REVEL
Pathogenic
Sift
Uncertain
D;D;.
Sift4G
Uncertain
D;D;D
Polyphen
D;D;D
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at