1-113093555-T-C
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Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_014813.3(LRIG2):āc.506T>Cā(p.Leu169Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000193 in 1,602,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.0000067 ( 0 hom., cov: 30)
Exomes š: 0.000021 ( 0 hom. )
Consequence
LRIG2
NM_014813.3 missense
NM_014813.3 missense
Scores
13
4
2
Clinical Significance
Conservation
PhyloP100: 7.63
Genes affected
LRIG2 (HGNC:20889): (leucine rich repeats and immunoglobulin like domains 2) This gene encodes a transmembrane protein containing leucine-rich repeats and immunoglobulin-like domains. The encoded protein promotes epidermal growth factor signalling, resulting in increased proliferation. Its expression in the cytoplasm of glioma cells is correlated with poor survival. Mutations in this gene can cause urofacial syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2015]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.955
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LRIG2 | NM_014813.3 | c.506T>C | p.Leu169Pro | missense_variant | 4/18 | ENST00000361127.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRIG2 | ENST00000361127.6 | c.506T>C | p.Leu169Pro | missense_variant | 4/18 | 1 | NM_014813.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000673 AC: 1AN: 148632Hom.: 0 Cov.: 30
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GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251174Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135822
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GnomAD4 exome AF: 0.0000206 AC: 30AN: 1454172Hom.: 0 Cov.: 31 AF XY: 0.0000193 AC XY: 14AN XY: 723558
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GnomAD4 genome AF: 0.00000673 AC: 1AN: 148632Hom.: 0 Cov.: 30 AF XY: 0.0000139 AC XY: 1AN XY: 72112
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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 | Nov 15, 2021 | The c.506T>C (p.L169P) alteration is located in exon 4 (coding exon 4) of the LRIG2 gene. This alteration results from a T to C substitution at nucleotide position 506, causing the leucine (L) at amino acid position 169 to be replaced by a proline (P). 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
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D
REVEL
Pathogenic
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MutPred
Gain of disorder (P = 0.0116);
MVP
MPC
ClinPred
D
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