chr17-75569090-T-C

Position:

• chr17-75569090-T-C

Variant summary

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

The NM_001031803.2(LLGL2):​c.1435T>C​(p.Phe479Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 1,612,362 control chromosomes in the GnomAD database, including 128,083 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 0.49 (21364 hom., cov: 33)
  • Exomes 𝑓: 0.37 (106719 hom.)
• Consequence: LLGL2 NM_001031803.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.05

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.281977E-7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.817 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LLGL2	NM_001031803.2	c.1435T>C	p.Phe479Leu	missense_variant	13/26	ENST00000392550.8	NP_001026973.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LLGL2	ENST00000392550.8	c.1435T>C	p.Phe479Leu	missense_variant	13/26	1	NM_001031803.2	ENSP00000376333.4

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73674 AN: 151990 Hom.: 21314 Cov.: 33

Gnomad AFR AF: 0.824

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.424

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.449

GnomAD3 exomes AF: 0.361 AC: 89446 AN: 247438 Hom.: 18635 AF XY: 0.353 AC XY: 47307 AN XY: 134148

Gnomad AFR exome AF: 0.843

Gnomad AMR exome AF: 0.265

Gnomad ASJ exome AF: 0.411

Gnomad EAS exome AF: 0.205

Gnomad SAS exome AF: 0.263

Gnomad FIN exome AF: 0.330

Gnomad NFE exome AF: 0.376

Gnomad OTH exome AF: 0.366

GnomAD4 exome AF: 0.371 AC: 542153 AN: 1460254 Hom.: 106719 Cov.: 54 AF XY: 0.367 AC XY: 266836 AN XY: 726402

Gnomad4 AFR exome AF: 0.853

Gnomad4 AMR exome AF: 0.275

Gnomad4 ASJ exome AF: 0.408

Gnomad4 EAS exome AF: 0.168

Gnomad4 SAS exome AF: 0.268

Gnomad4 FIN exome AF: 0.331

Gnomad4 NFE exome AF: 0.376

Gnomad4 OTH exome AF: 0.388

GnomAD4 genome AF: 0.485 AC: 73779 AN: 152108 Hom.: 21364 Cov.: 33 AF XY: 0.474 AC XY: 35245 AN XY: 74352

Gnomad4 AFR AF: 0.825

Gnomad4 AMR AF: 0.338

Gnomad4 ASJ AF: 0.424

Gnomad4 EAS AF: 0.206

Gnomad4 SAS AF: 0.260

Gnomad4 FIN AF: 0.339

Gnomad4 NFE AF: 0.375

Gnomad4 OTH AF: 0.446

Alfa AF: 0.395 Hom.: 25978

Bravo AF: 0.503

TwinsUK AF: 0.375 AC: 1390

ALSPAC AF: 0.373 AC: 1439

ESP6500AA AF: 0.824 AC: 3630

ESP6500EA AF: 0.386 AC: 3320

ExAC AF: 0.371 AC: 45035

Asia WGS AF: 0.285 AC: 992 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	15
DANN	Benign	0.96
DEOGEN2	Benign	0.011	.;T;.
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.050	T;T;T
MetaRNN	Benign	7.3e-7	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.9	N;N;.
PrimateAI	Benign	0.47	T
PROVEAN	Benign	1.3	N;N;.
REVEL	Benign	0.12
Sift	Benign	0.79	T;T;.
Sift4G	Benign	0.72	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.022
MutPred		0.10		Gain of sheet (P = 0.0028);Gain of sheet (P = 0.0028);Gain of sheet (P = 0.0028);
MPC		0.26
ClinPred		0.0095	T
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.060
gMVP		0.17

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: rs1671021; hg19: chr17-73565171; COSMIC: COSV51350886; COSMIC: COSV51350886;