Genetic Variant LLGL2:p.Val104Ile (chr17-75558566-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001031803.2(LLGL2):c.310G>A(p.Val104Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,459,510 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. V104F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

LLGL2
NM_001031803.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.03

Publications

1 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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10572803).

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.310G>A	p.Val104Ile	missense	Exon 5 of 26	NP_001026973.1	Q6P1M3-1
LLGL2	NM_004524.3		c.310G>A	p.Val104Ile	missense	Exon 5 of 25	NP_004515.2	Q6P1M3-2
LLGL2	NM_001015002.2		c.310G>A	p.Val104Ile	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.310G>A	p.Val104Ile	missense	Exon 5 of 26	ENSP00000376333.4	Q6P1M3-1
LLGL2	ENST00000577200.5	TSL:1	c.310G>A	p.Val104Ile	missense	Exon 5 of 26	ENSP00000464397.1	J3QRV5
LLGL2	ENST00000167462.9	TSL:1	c.310G>A	p.Val104Ile	missense	Exon 5 of 25	ENSP00000167462.5	Q6P1M3-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000122

AC:

AN:

246372

AF XY:

0.0000225

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1459510

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

725800

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33436

American (AMR)

AF:

0.00

AC:

AN:

44498

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26080

East Asian (EAS)

AF:

0.00

AC:

AN:

39626

South Asian (SAS)

AF:

0.0000584

AC:

AN:

85640

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53082

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5728

European-Non Finnish (NFE)

AF:

0.00000810

AC:

AN:

1111156

Other (OTH)

AF:

0.0000166

AC:

AN:

60264

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

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

Cov.:

ExAC

AF:

0.0000247

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.18

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.020

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.57

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.62

M_CAP

Benign

0.046

MetaRNN

Benign

0.11

MetaSVM

Uncertain

-0.19

MutationAssessor

Benign

0.69

PhyloP100

3.0

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.35

REVEL

Benign

0.038

Sift

Benign

0.20

Sift4G

Benign

0.55

Polyphen

0.0010

Vest4

0.078

MutPred

0.27

Gain of catalytic residue at V104 (P = 0.0368)

MVP

0.50

MPC

0.18

ClinPred

0.052

GERP RS

0.89

Varity_R

0.060

gMVP

0.22

Mutation Taster

=90/10

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over