chr17-75558530-C-G

Variant names:

• chr17-75558530-C-G
• rs766986353
• NM_001031803.2:c.274C>G

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001031803.2(LLGL2):​c.274C>G​(p.Leu92Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000998 in 1,603,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: LLGL2 NM_001031803.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.54
• 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 -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.38291985).

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.274C>G	p.Leu92Val	missense	Exon 5 of 26	NP_001026973.1	Q6P1M3-1
	LLGL2	NM_004524.3		c.274C>G	p.Leu92Val	missense	Exon 5 of 25	NP_004515.2	Q6P1M3-2
	LLGL2	NM_001015002.2		c.274C>G	p.Leu92Val	missense	Exon 5 of 10	NP_001015002.1	Q6P1M3-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LLGL2	ENST00000392550.8	TSL:1 MANE Select	c.274C>G	p.Leu92Val	missense	Exon 5 of 26	ENSP00000376333.4	Q6P1M3-1
	LLGL2	ENST00000577200.5	TSL:1	c.274C>G	p.Leu92Val	missense	Exon 5 of 26	ENSP00000464397.1	J3QRV5
	LLGL2	ENST00000167462.9	TSL:1	c.274C>G	p.Leu92Val	missense	Exon 5 of 25	ENSP00000167462.5	Q6P1M3-2

Frequencies

GnomAD3 genomes AF: 0.0000592 AC: 9 AN: 152116 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000523

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: 0.000478

GnomAD2 exomes AF: 0.0000128 AC: 3 AN: 234572 AF XY: 0.0000236

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000309

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000482 AC: 7 AN: 1451754 Hom.: 0 Cov.: 31 AF XY: 0.00000693 AC XY: 5 AN XY: 721288

African (AFR) AF: 0.00 AC: 0 AN: 33228

American (AMR) AF: 0.0000230 AC: 1 AN: 43530

Ashkenazi Jewish (ASJ) AF: 0.000116 AC: 3 AN: 25940

East Asian (EAS) AF: 0.00 AC: 0 AN: 39112

South Asian (SAS) AF: 0.00 AC: 0 AN: 84166

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52282

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1107788

Other (OTH) AF: 0.0000167 AC: 1 AN: 59962

GnomAD4 genome AF: 0.0000592 AC: 9 AN: 152116 Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6 AN XY: 74310

African (AFR) AF: 0.00 AC: 0 AN: 41412

American (AMR) AF: 0.000523 AC: 8 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67990

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.0000451 Hom.: 0

Bravo AF: 0.0000982

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Benign	0.13	T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.067	D
MetaRNN	Benign	0.38	T
MetaSVM	Uncertain	-0.20	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		1.5
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.8	N
REVEL	Uncertain	0.37
Sift	Benign	0.063	T
Sift4G	Uncertain	0.013	D
Polyphen		0.99	D
Vest4		0.71
MutPred		0.60		Loss of sheet (P = 0.1158)
MVP		0.68
MPC		0.84
ClinPred		0.66	D
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.47
gMVP		0.51
Mutation Taster		=70/30	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs766986353; hg19: chr17-73554611;