dbSNP rs6501822: LLGL2:c.75+49A>G (chr17-75543550-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001031803.2(LLGL2):c.75+49A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.887 in 1,532,964 control chromosomes in the GnomAD database, including 607,727 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.85 ( 55151 hom., cov: 32)

Exomes 𝑓: 0.89 ( 552576 hom. )

Consequence

LLGL2
NM_001031803.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.154

Publications

18 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.907 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LLGL2	NM_001031803.2 link	c.75+49A>G		intron_variant	Intron 2 of 25	ENST00000392550.8	NP_001026973.1	Q6P1M3-1A0PJJ0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LLGL2	ENST00000392550.8 link	c.75+49A>G		intron_variant	Intron 2 of 25	1	NM_001031803.2	ENSP00000376333.4		Q6P1M3-1

Frequencies

GnomAD3 genomes

AF:

0.848

AC:

128886

AN:

152044

Hom.:

55103

Cov.:

show subpopulations

Gnomad AFR

AF:

0.779

Gnomad AMI

AF:

0.941

Gnomad AMR

AF:

0.745

Gnomad ASJ

AF:

0.846

Gnomad EAS

AF:

0.679

Gnomad SAS

AF:

0.871

Gnomad FIN

AF:

0.907

Gnomad MID

AF:

0.927

Gnomad NFE

AF:

0.913

Gnomad OTH

AF:

0.849

GnomAD2 exomes

AF:

0.836

AC:

190310

AN:

227662

AF XY:

0.852

show subpopulations

Gnomad AFR exome

AF:

0.775

Gnomad AMR exome

AF:

0.595

Gnomad ASJ exome

AF:

0.835

Gnomad EAS exome

AF:

0.665

Gnomad FIN exome

AF:

0.907

Gnomad NFE exome

AF:

0.915

Gnomad OTH exome

AF:

0.867

GnomAD4 exome

AF:

0.891

AC:

1230969

AN:

1380802

Hom.:

552576

Cov.:

AF XY:

0.893

AC XY:

614997

AN XY:

688458

show subpopulations

African (AFR)

AF:

0.776

AC:

24476

AN:

31534

American (AMR)

AF:

0.615

AC:

25400

AN:

41326

Ashkenazi Jewish (ASJ)

AF:

0.839

AC:

20511

AN:

24436

East Asian (EAS)

AF:

0.648

AC:

24828

AN:

38324

South Asian (SAS)

AF:

0.885

AC:

71548

AN:

80878

European-Finnish (FIN)

AF:

0.908

AC:

47522

AN:

52358

Middle Eastern (MID)

AF:

0.922

AC:

5108

AN:

5540

European-Non Finnish (NFE)

AF:

0.916

AC:

961340

AN:

1049026

Other (OTH)

AF:

0.875

AC:

50236

AN:

57380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

5827

11654

17481

23308

29135

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20072

40144

60216

80288

100360

<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:

0.848

AC:

128992

AN:

152162

Hom.:

55151

Cov.:

AF XY:

0.846

AC XY:

62960

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.779

AC:

32331

AN:

41480

American (AMR)

AF:

0.745

AC:

11387

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.846

AC:

2935

AN:

3470

East Asian (EAS)

AF:

0.679

AC:

3516

AN:

5176

South Asian (SAS)

AF:

0.871

AC:

4205

AN:

4826

European-Finnish (FIN)

AF:

0.907

AC:

9613

AN:

10598

Middle Eastern (MID)

AF:

0.922

AC:

271

AN:

294

European-Non Finnish (NFE)

AF:

0.913

AC:

62089

AN:

68020

Other (OTH)

AF:

0.850

AC:

1791

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

980

1960

2941

3921

4901

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

890

1780

2670

3560

4450

<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:

0.882

Hom.:

166016

Bravo

AF:

0.826

Asia WGS

AF:

0.807

AC:

2806

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.52

(source)

DANN

Benign

0.21

PhyloP100

0.15

PromoterAI

-0.0032

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over