Variant 17-75556104-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001031803.2(LLGL2):c.134G>A(p.Arg45His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 1,609,404 control chromosomes in the GnomAD database, including 232,210 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.43 ( 16485 hom., cov: 32)

Exomes 𝑓: 0.54 ( 215725 hom. )

Consequence

LLGL2
NM_001031803.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.42

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.6456906E-5).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.591 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LLGL2	NM_001031803.2 linkuse as main transcript	c.134G>A	p.Arg45His	missense_variant	3/26	ENST00000392550.8	NP_001026973.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LLGL2	ENST00000392550.8 linkuse as main transcript	c.134G>A	p.Arg45His	missense_variant	3/26	1	NM_001031803.2	ENSP00000376333	P4	Q6P1M3-1

Frequencies

GnomAD3 genomes

AF:

0.434

AC:

65884

AN:

151954

Hom.:

16484

Cov.:

show subpopulations

Gnomad AFR

AF:

0.169

Gnomad AMI

AF:

0.554

Gnomad AMR

AF:

0.425

Gnomad ASJ

AF:

0.562

Gnomad EAS

AF:

0.470

Gnomad SAS

AF:

0.610

Gnomad FIN

AF:

0.532

Gnomad MID

AF:

0.541

Gnomad NFE

AF:

0.556

Gnomad OTH

AF:

0.474

GnomAD3 exomes

AF:

0.501

AC:

124162

AN:

248074

Hom.:

33164

AF XY:

0.522

AC XY:

70220

AN XY:

134552

show subpopulations

Gnomad AFR exome

AF:

0.158

Gnomad AMR exome

AF:

0.350

Gnomad ASJ exome

AF:

0.564

Gnomad EAS exome

AF:

0.449

Gnomad SAS exome

AF:

0.628

Gnomad FIN exome

AF:

0.539

Gnomad NFE exome

AF:

0.556

Gnomad OTH exome

AF:

0.522

GnomAD4 exome

AF:

0.538

AC:

784332

AN:

1457332

Hom.:

215725

Cov.:

AF XY:

0.544

AC XY:

394401

AN XY:

725286

show subpopulations

Gnomad4 AFR exome

AF:

0.150

Gnomad4 AMR exome

AF:

0.360

Gnomad4 ASJ exome

AF:

0.568

Gnomad4 EAS exome

AF:

0.460

Gnomad4 SAS exome

AF:

0.623

Gnomad4 FIN exome

AF:

0.541

Gnomad4 NFE exome

AF:

0.553

Gnomad4 OTH exome

AF:

0.526

GnomAD4 genome

AF:

0.433

AC:

65903

AN:

152072

Hom.:

16485

Cov.:

AF XY:

0.435

AC XY:

32332

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.169

Gnomad4 AMR

AF:

0.425

Gnomad4 ASJ

AF:

0.562

Gnomad4 EAS

AF:

0.469

Gnomad4 SAS

AF:

0.609

Gnomad4 FIN

AF:

0.532

Gnomad4 NFE

AF:

0.556

Gnomad4 OTH

AF:

0.477

Alfa

AF:

0.530

Hom.:

28057

Bravo

AF:

0.407

TwinsUK

AF:

0.554

AC:

2053

ALSPAC

AF:

0.548

AC:

2113

ESP6500AA

AF:

0.176

AC:

774

ESP6500EA

AF:

0.550

AC:

4733

ExAC

AF:

0.501

AC:

60778

Asia WGS

AF:

0.535

AC:

1863

AN:

3478

EpiCase

AF:

0.563

EpiControl

AF:

0.567

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.10

T;.;.;T;.;T;.;T;T;.

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.84

T;D;.;D;D;D;D;D;T;T

MetaRNN

Benign

0.000026

T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.49

.;N;N;N;N;.;.;.;.;.

MutationTaster

Benign

0.87

P;P;P;P;P

PrimateAI

Benign

0.26

PROVEAN

Uncertain

-2.7

.;D;D;D;.;.;.;.;.;.

REVEL

Benign

0.058

Sift

Benign

0.069

.;T;T;T;.;.;.;.;.;.

Sift4G

Benign

0.15

T;T;T;T;T;T;T;T;T;T

Polyphen

0.054, 0.0060, 0.0030

.;B;B;B;B;.;.;.;.;.

Vest4

0.071, 0.12, 0.072, 0.12, 0.070

MPC

0.28

ClinPred

0.0067

GERP RS

3.6

Varity_R

0.31

gMVP

0.37

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over