chr15-77614522-C-T
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2PP2BP4_Strong
The NM_032808.7(LINGO1):c.1385G>A(p.Arg462Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000472 in 1,610,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000025 ( 0 hom. )
Consequence
LINGO1
NM_032808.7 missense
NM_032808.7 missense
Scores
3
16
Clinical Significance
Conservation
PhyloP100: 4.89
Genes affected
LINGO1 (HGNC:21205): (leucine rich repeat and Ig domain containing 1) Predicted to enable epidermal growth factor receptor binding activity. Predicted to act upstream of or within generation of neurons and protein kinase B signaling. Predicted to be located in plasma membrane. Predicted to be active in extracellular matrix and extracellular space. Implicated in autosomal recessive non-syndromic intellectual disability and glaucoma. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, LINGO1
BP4
?
Computational evidence support a benign effect (MetaRNN=0.05477032).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LINGO1 | NM_032808.7 | c.1385G>A | p.Arg462Gln | missense_variant | 2/2 | ENST00000355300.7 | |
LOC105370906 | XR_001751806.2 | n.689-15763C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LINGO1 | ENST00000355300.7 | c.1385G>A | p.Arg462Gln | missense_variant | 2/2 | 1 | NM_032808.7 | A1 | |
LINGO1 | ENST00000561030.5 | c.1367G>A | p.Arg456Gln | missense_variant | 4/4 | 1 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000263 AC: 40AN: 152252Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000291 AC: 7AN: 240920Hom.: 0 AF XY: 0.0000152 AC XY: 2AN XY: 131890
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GnomAD4 exome AF: 0.0000247 AC: 36AN: 1458412Hom.: 0 Cov.: 31 AF XY: 0.0000165 AC XY: 12AN XY: 725608
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GnomAD4 genome ? AF: 0.000263 AC: 40AN: 152370Hom.: 0 Cov.: 33 AF XY: 0.000148 AC XY: 11AN XY: 74508
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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 | Apr 25, 2023 | The c.1385G>A (p.R462Q) alteration is located in exon 2 (coding exon 2) of the LINGO1 gene. This alteration results from a G to A substitution at nucleotide position 1385, causing the arginine (R) at amino acid position 462 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Benign
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;.
Vest4
MutPred
Loss of MoRF binding (P = 0.0569);.;
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at