Genetic Variant NM_001031803.2:c.319G>A (chr17-75558575-G-A) – 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>A(p.Gly107Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000372 in 1,611,542 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

LLGL2
NM_001031803.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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:

Genome browser will be placed here

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>A	p.Gly107Arg	missense	Exon 5 of 26	NP_001026973.1	Q6P1M3-1
LLGL2	NM_004524.3		c.319G>A	p.Gly107Arg	missense	Exon 5 of 25	NP_004515.2	Q6P1M3-2
LLGL2	NM_001015002.2		c.319G>A	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>A	p.Gly107Arg	missense	Exon 5 of 26	ENSP00000376333.4	Q6P1M3-1
LLGL2	ENST00000577200.5	TSL:1	c.319G>A	p.Gly107Arg	missense	Exon 5 of 26	ENSP00000464397.1	J3QRV5
LLGL2	ENST00000167462.9	TSL:1	c.319G>A	p.Gly107Arg	missense	Exon 5 of 25	ENSP00000167462.5	Q6P1M3-2

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000325

AC:

AN:

246152

AF XY:

0.0000150

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000631

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000384

AC:

AN:

1459438

Hom.:

Cov.:

AF XY:

0.0000331

AC XY:

AN XY:

725766

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:

0.0000350

AC:

AN:

85656

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53096

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5686

European-Non Finnish (NFE)

AF:

0.0000459

AC:

AN:

1111126

Other (OTH)

AF:

0.0000332

AC:

AN:

60258

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152104

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41404

American (AMR)

AF:

0.00

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68004

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000772

Hom.:

Bravo

AF:

0.0000340

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000495

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

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

Uncertain

(source)

DANN

Benign

0.48

DEOGEN2

Benign

0.067

Eigen

Benign

0.014

Eigen_PC

Benign

-0.13

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.81

M_CAP

Uncertain

0.17

MetaRNN

Uncertain

0.69

MetaSVM

Uncertain

0.45

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

0.77

GERP RS

3.3

Varity_R

0.39

gMVP

0.71

Mutation Taster

=73/27

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over