rs6501822

Positions:

• chr17-75543550-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000392550.8(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 ENST00000392550.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.154

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
LLGL2	NM_001031803.2	c.75+49A>G		intron_variant		ENST00000392550.8	NP_001026973.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LLGL2	ENST00000392550.8	c.75+49A>G		intron_variant		1	NM_001031803.2	ENSP00000376333	P4

Frequencies

GnomAD3 genomes AF: 0.848 AC: 128886 AN: 152044 Hom.: 55103 Cov.: 32

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

GnomAD3 exomes AF: 0.836 AC: 190310 AN: 227662 Hom.: 81262 AF XY: 0.852 AC XY: 105071 AN XY: 123388

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 SAS exome AF: 0.884

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.: 18 AF XY: 0.893 AC XY: 614997 AN XY: 688458

Gnomad4 AFR exome AF: 0.776

Gnomad4 AMR exome AF: 0.615

Gnomad4 ASJ exome AF: 0.839

Gnomad4 EAS exome AF: 0.648

Gnomad4 SAS exome AF: 0.885

Gnomad4 FIN exome AF: 0.908

Gnomad4 NFE exome AF: 0.916

Gnomad4 OTH exome AF: 0.875

GnomAD4 genome AF: 0.848 AC: 128992 AN: 152162 Hom.: 55151 Cov.: 32 AF XY: 0.846 AC XY: 62960 AN XY: 74398

Gnomad4 AFR AF: 0.779

Gnomad4 AMR AF: 0.745

Gnomad4 ASJ AF: 0.846

Gnomad4 EAS AF: 0.679

Gnomad4 SAS AF: 0.871

Gnomad4 FIN AF: 0.907

Gnomad4 NFE AF: 0.913

Gnomad4 OTH AF: 0.850

Alfa AF: 0.894 Hom.: 99090

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
DANN	Benign	0.21

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

Other links and lift over

dbSNP: rs6501822; hg19: chr17-73539631; COSMIC: COSV51344478; COSMIC: COSV51344478;