Genetic Variant NM_001031803.2:c.319G>C (chr17-75558575-G-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001031803.2(LLGL2):c.319G>C(p.Gly107Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,440 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

LLGL2
NM_001031803.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.88

Publications

0 publications found

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]

LLGL2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001031803.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LLGL2	NM_001031803.2	MANE Select	c.319G>C	p.Gly107Arg	missense	Exon 5 of 26	NP_001026973.1	Q6P1M3-1
LLGL2	NM_004524.3		c.319G>C	p.Gly107Arg	missense	Exon 5 of 25	NP_004515.2	Q6P1M3-2
LLGL2	NM_001015002.2		c.319G>C	p.Gly107Arg	missense	Exon 5 of 10	NP_001015002.1	Q6P1M3-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LLGL2	ENST00000392550.8	TSL:1 MANE Select	c.319G>C	p.Gly107Arg	missense	Exon 5 of 26	ENSP00000376333.4	Q6P1M3-1
LLGL2	ENST00000577200.5	TSL:1	c.319G>C	p.Gly107Arg	missense	Exon 5 of 26	ENSP00000464397.1	J3QRV5
LLGL2	ENST00000167462.9	TSL:1	c.319G>C	p.Gly107Arg	missense	Exon 5 of 25	ENSP00000167462.5	Q6P1M3-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459440

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725768

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33424

American (AMR)

AF:

0.00

AC:

AN:

44498

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26084

East Asian (EAS)

AF:

0.00

AC:

AN:

39610

South Asian (SAS)

AF:

0.00

AC:

AN:

85658

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53096

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5686

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111126

Other (OTH)

AF:

0.00

AC:

AN:

60258

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Pathogenic

0.31

BayesDel_noAF

Pathogenic

0.20

CADD

Benign

(source)

DANN

Benign

0.46

DEOGEN2

Benign

0.067

Eigen

Benign

0.028

Eigen_PC

Benign

-0.12

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.81

M_CAP

Uncertain

0.17

MetaRNN

Uncertain

0.74

MetaSVM

Uncertain

0.46

MutationAssessor

Uncertain

2.5

PhyloP100

3.9

PrimateAI

Uncertain

0.62

PROVEAN

Pathogenic

-4.5

REVEL

Benign

0.28

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.0050

Polyphen

1.0

Vest4

0.60

MutPred

0.39

Loss of catalytic residue at G107 (P = 0.029)

MVP

0.91

MPC

0.53

ClinPred

0.99

GERP RS

3.3

Varity_R

0.39

gMVP

0.71

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over