LLGL2 p.Phe479Leu

Variant names:

• chr17-75569092-C-A
• NM_001031803.2:c.1437C>A
• LLGL2 p.Phe479Leu

Your query was ambiguous. Multiple possible variants found:

• chr17-75569092-C-A
• chr17-75569092-C-G
• chr17-75569090-T-C
• chr17-75569090-TTC-CTT
• chr17-75569090-TTC-CTA
• chr17-75569090-TTC-CTG

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001031803.2(LLGL2):​c.1437C>A​(p.Phe479Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 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. F479V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: LLGL2 NM_001031803.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.26
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05504322).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LLGL2	NM_001031803.2	MANE Select	c.1437C>A	p.Phe479Leu	missense	Exon 13 of 26	NP_001026973.1	Q6P1M3-1
	LLGL2	NM_004524.3		c.1437C>A	p.Phe479Leu	missense	Exon 13 of 25	NP_004515.2	Q6P1M3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LLGL2	ENST00000392550.8	TSL:1 MANE Select	c.1437C>A	p.Phe479Leu	missense	Exon 13 of 26	ENSP00000376333.4	Q6P1M3-1
	LLGL2	ENST00000577200.5	TSL:1	c.1437C>A	p.Phe479Leu	missense	Exon 13 of 26	ENSP00000464397.1	J3QRV5
	LLGL2	ENST00000167462.9	TSL:1	c.1437C>A	p.Phe479Leu	missense	Exon 13 of 25	ENSP00000167462.5	Q6P1M3-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 39

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	10
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.51
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.050	T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-1.9	N
PhyloP100		3.3
PrimateAI	Benign	0.47	T
PROVEAN	Benign	1.3	N
REVEL	Benign	0.12
Sift	Benign	0.79	T
Sift4G	Benign	0.72	T
Varity_R		0.068
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr17-73565173;