17-75556104-G-C

Position:

• chr17-75556104-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001031803.2(LLGL2):​c.134G>C​(p.Arg45Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. R45H) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: LLGL2 NM_001031803.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.42

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LLGL2	NM_001031803.2	c.134G>C	p.Arg45Pro	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	c.134G>C	p.Arg45Pro	missense_variant	3/26	1	NM_001031803.2	ENSP00000376333.4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 151996 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 47

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 151996 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74228

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.54
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	20
DANN	Benign	0.71
DEOGEN2	Benign	0.22	T;.;.;T;.;T;.;T;T;.
Eigen	Benign	0.023
Eigen_PC	Benign	-0.041
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Uncertain	0.88	D;D;.;D;D;D;D;D;D;D
M_CAP	Benign	0.078	D
MetaRNN	Uncertain	0.53	D;D;D;D;D;D;D;D;D;D
MetaSVM	Uncertain	-0.24	T
MutationAssessor	Benign	1.6	.;L;L;L;L;.;.;.;.;.
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-4.1	.;D;D;D;.;.;.;.;.;.
REVEL	Benign	0.15
Sift	Uncertain	0.0040	.;D;D;D;.;.;.;.;.;.
Sift4G	Uncertain	0.028	D;D;T;D;T;D;D;D;D;D
Polyphen		0.92, 0.72, 0.60	.;P;P;P;P;.;.;.;.;.
Vest4		0.70, 0.70, 0.70, 0.70
MutPred		0.50		Loss of MoRF binding (P = 0.0175);Loss of MoRF binding (P = 0.0175);Loss of MoRF binding (P = 0.0175);Loss of MoRF binding (P = 0.0175);Loss of MoRF binding (P = 0.0175);Loss of MoRF binding (P = 0.0175);Loss of MoRF binding (P = 0.0175);Loss of MoRF binding (P = 0.0175);Loss of MoRF binding (P = 0.0175);.;
MVP		0.73
MPC		0.44
ClinPred		0.88	D
GERP RS		3.6
Varity_R		0.89
gMVP		0.74

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: rs1671036; hg19: chr17-73552185;