NM_001031803.2:c.37C>T

Variant names:

• chr17-75543463-C-T
• rs749734318
• NM_001031803.2:c.37C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001031803.2(LLGL2):​c.37C>T​(p.Arg13Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,459,616 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: LLGL2 NM_001031803.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.245
• Publications: 1 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: Uncertain_significance. The variant received 2 ACMG points.

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

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.37C>T	p.Arg13Trp	missense	Exon 2 of 26	NP_001026973.1	Q6P1M3-1
	LLGL2	NM_004524.3		c.37C>T	p.Arg13Trp	missense	Exon 2 of 25	NP_004515.2	Q6P1M3-2
	LLGL2	NM_001015002.2		c.37C>T	p.Arg13Trp	missense	Exon 2 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.37C>T	p.Arg13Trp	missense	Exon 2 of 26	ENSP00000376333.4	Q6P1M3-1
	LLGL2	ENST00000577200.5	TSL:1	c.37C>T	p.Arg13Trp	missense	Exon 2 of 26	ENSP00000464397.1	J3QRV5
	LLGL2	ENST00000167462.9	TSL:1	c.37C>T	p.Arg13Trp	missense	Exon 2 of 25	ENSP00000167462.5	Q6P1M3-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000802 AC: 2 AN: 249382 AF XY: 0.00000741

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000116 AC: 17 AN: 1459616 Hom.: 0 Cov.: 30 AF XY: 0.0000110 AC XY: 8 AN XY: 726006

African (AFR) AF: 0.000120 AC: 4 AN: 33406

American (AMR) AF: 0.00 AC: 0 AN: 44456

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39566

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 85946

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53360

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.0000108 AC: 12 AN: 1110760

Other (OTH) AF: 0.00 AC: 0 AN: 60266

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000312 Hom.: 0

ExAC AF: 0.0000165 AC: 2

Asia WGS AF: 0.000577 AC: 2 AN: 3478

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	0.52
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Benign	22
DANN	Benign	0.79
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.054	N
LIST_S2	Pathogenic	0.97	D
M_CAP	Uncertain	0.26	D
MetaRNN	Uncertain	0.64	D
MetaSVM	Uncertain	0.69	D
MutationAssessor	Uncertain	2.6	M
PhyloP100		-0.24
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Uncertain	0.56
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.56
MutPred		0.48		Loss of disorder (P = 0)
MVP		0.92
MPC		0.84
ClinPred		0.98	D
GERP RS		-4.5
PromoterAI		-0.011	Neutral
Varity_R		0.83
gMVP		0.66
Mutation Taster		=84/16	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs749734318; hg19: chr17-73539544; COSMIC: COSV51341705; COSMIC: COSV51341705;