1-113073626-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_014813.3(LRIG2):​c.220C>G​(p.Pro74Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,314 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P74T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

LRIG2
NM_014813.3 missense

Scores

4
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.15
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.31266212).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LRIG2NM_014813.3 linkc.220C>G p.Pro74Ala missense_variant Exon 1 of 18 ENST00000361127.6 NP_055628.1 O94898
LRIG2XM_005271369.3 linkc.220C>G p.Pro74Ala missense_variant Exon 1 of 17 XP_005271426.1
LRIG2NM_001312686.2 linkc.-202C>G 5_prime_UTR_variant Exon 1 of 19 NP_001299615.1 O94898

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LRIG2ENST00000361127.6 linkc.220C>G p.Pro74Ala missense_variant Exon 1 of 18 1 NM_014813.3 ENSP00000355396.4 O94898

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460314
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
726494
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.28
BayesDel_addAF
Uncertain
0.062
T
BayesDel_noAF
Benign
-0.15
CADD
Benign
22
DANN
Uncertain
0.98
DEOGEN2
Benign
0.12
T
Eigen
Benign
-0.20
Eigen_PC
Benign
-0.11
FATHMM_MKL
Benign
0.68
D
LIST_S2
Benign
0.56
T
M_CAP
Benign
0.031
D
MetaRNN
Benign
0.31
T
MetaSVM
Benign
-0.89
T
MutationAssessor
Benign
0.69
N
PrimateAI
Benign
0.41
T
PROVEAN
Benign
-2.1
N
REVEL
Benign
0.17
Sift
Uncertain
0.016
D
Sift4G
Uncertain
0.016
D
Polyphen
0.032
B
Vest4
0.44
MutPred
0.52
Loss of disorder (P = 0.0744);
MVP
0.77
MPC
0.46
ClinPred
0.93
D
GERP RS
4.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.9
Varity_R
0.16
gMVP
0.55

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-113616248; API