17-75543463-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001031803.2(LLGL2):​c.37C>G​(p.Arg13Gly) 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 1,459,618 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R13W) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.9e-7 ( 0 hom. )

Consequence

LLGL2
NM_001031803.2 missense

Scores

3
10
6

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.245
Variant links:
Genes affected
LLGL2 (HGNC:6629): (LLGL scribble cell polarity complex component 2) The lethal (2) giant larvae protein of Drosophila plays a role in asymmetric cell division, epithelial cell polarity, and cell migration. This human gene encodes a protein similar to lethal (2) giant larvae of Drosophila. In fly, the protein's ability to localize cell fate determinants is regulated by the atypical protein kinase C (aPKC). In human, this protein interacts with aPKC-containing complexes and is cortically localized in mitotic cells. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LLGL2NM_001031803.2 linkc.37C>G p.Arg13Gly missense_variant Exon 2 of 26 ENST00000392550.8 NP_001026973.1 Q6P1M3-1A0PJJ0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LLGL2ENST00000392550.8 linkc.37C>G p.Arg13Gly missense_variant Exon 2 of 26 1 NM_001031803.2 ENSP00000376333.4 Q6P1M3-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1459618
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
726006
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:
9.00e-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
Pathogenic
0.57
BayesDel_addAF
Pathogenic
0.30
D
BayesDel_noAF
Pathogenic
0.20
CADD
Benign
20
DANN
Benign
0.87
DEOGEN2
Benign
0.097
T;.;.;T;.;T;.;T;T;T
Eigen
Benign
-0.27
Eigen_PC
Benign
-0.56
FATHMM_MKL
Benign
0.071
N
LIST_S2
Uncertain
0.94
D;D;.;D;D;D;D;D;D;D
M_CAP
Uncertain
0.23
D
MetaRNN
Uncertain
0.55
D;D;D;D;D;D;D;D;D;D
MetaSVM
Uncertain
0.69
D
MutationAssessor
Uncertain
2.6
.;M;M;M;M;.;.;.;.;.
PrimateAI
Uncertain
0.59
T
PROVEAN
Uncertain
-3.6
.;D;D;D;.;.;.;.;.;.
REVEL
Uncertain
0.58
Sift
Uncertain
0.0010
.;D;D;D;.;.;.;.;.;.
Sift4G
Uncertain
0.0070
D;D;D;D;D;D;D;D;D;D
Polyphen
1.0, 0.98
.;D;D;D;D;.;.;.;.;.
Vest4
0.65, 0.74, 0.68, 0.65
MutPred
0.42
Loss of MoRF binding (P = 0.0152);Loss of MoRF binding (P = 0.0152);Loss of MoRF binding (P = 0.0152);Loss of MoRF binding (P = 0.0152);Loss of MoRF binding (P = 0.0152);Loss of MoRF binding (P = 0.0152);Loss of MoRF binding (P = 0.0152);Loss of MoRF binding (P = 0.0152);Loss of MoRF binding (P = 0.0152);Loss of MoRF binding (P = 0.0152);
MVP
0.95
MPC
0.90
ClinPred
0.99
D
GERP RS
-4.5
Varity_R
0.92
gMVP
0.65

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.090
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: chr17-73539544; API