rs1671036

Variant names:

• chr17-75556104-G-A
• rs1671036
• NM_001031803.2:c.134G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-75556104-G-A
• chr17-75556104-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001031803.2(LLGL2):​c.134G>A​(p.Arg45His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 1,609,404 control chromosomes in the GnomAD database, including 232,210 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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. R45C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.43 (16485 hom., cov: 32)
  • Exomes 𝑓: 0.54 (215725 hom.)
• Consequence: LLGL2 NM_001031803.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.42
• Publications: 36 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.6456906E-5).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.591 is higher than 0.05.

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.134G>A	p.Arg45His	missense	Exon 3 of 26	NP_001026973.1	Q6P1M3-1
	LLGL2	NM_004524.3		c.134G>A	p.Arg45His	missense	Exon 3 of 25	NP_004515.2	Q6P1M3-2
	LLGL2	NM_001015002.2		c.134G>A	p.Arg45His	missense	Exon 3 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.134G>A	p.Arg45His	missense	Exon 3 of 26	ENSP00000376333.4	Q6P1M3-1
	LLGL2	ENST00000577200.5	TSL:1	c.134G>A	p.Arg45His	missense	Exon 3 of 26	ENSP00000464397.1	J3QRV5
	LLGL2	ENST00000167462.9	TSL:1	c.134G>A	p.Arg45His	missense	Exon 3 of 25	ENSP00000167462.5	Q6P1M3-2

Frequencies

GnomAD3 genomes AF: 0.434 AC: 65884 AN: 151954 Hom.: 16484 Cov.: 32

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.562

Gnomad EAS AF: 0.470

Gnomad SAS AF: 0.610

Gnomad FIN AF: 0.532

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.556

Gnomad OTH AF: 0.474

GnomAD2 exomes AF: 0.501 AC: 124162 AN: 248074 AF XY: 0.522

Gnomad AFR exome AF: 0.158

Gnomad AMR exome AF: 0.350

Gnomad ASJ exome AF: 0.564

Gnomad EAS exome AF: 0.449

Gnomad FIN exome AF: 0.539

Gnomad NFE exome AF: 0.556

Gnomad OTH exome AF: 0.522

GnomAD4 exome AF: 0.538 AC: 784332 AN: 1457332 Hom.: 215725 Cov.: 47 AF XY: 0.544 AC XY: 394401 AN XY: 725286

African (AFR) AF: 0.150 AC: 5021 AN: 33480

American (AMR) AF: 0.360 AC: 16106 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.568 AC: 14839 AN: 26124

East Asian (EAS) AF: 0.460 AC: 18236 AN: 39684

South Asian (SAS) AF: 0.623 AC: 53762 AN: 86244

European-Finnish (FIN) AF: 0.541 AC: 26672 AN: 49304

Middle Eastern (MID) AF: 0.538 AC: 3105 AN: 5768

European-Non Finnish (NFE) AF: 0.553 AC: 614856 AN: 1111650

Other (OTH) AF: 0.526 AC: 31735 AN: 60360

GnomAD4 genome AF: 0.433 AC: 65903 AN: 152072 Hom.: 16485 Cov.: 32 AF XY: 0.435 AC XY: 32332 AN XY: 74332

African (AFR) AF: 0.169 AC: 7029 AN: 41498

American (AMR) AF: 0.425 AC: 6507 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.562 AC: 1950 AN: 3470

East Asian (EAS) AF: 0.469 AC: 2413 AN: 5144

South Asian (SAS) AF: 0.609 AC: 2935 AN: 4816

European-Finnish (FIN) AF: 0.532 AC: 5621 AN: 10574

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.556 AC: 37779 AN: 67962

Other (OTH) AF: 0.477 AC: 1006 AN: 2110

Alfa AF: 0.515 Hom.: 64262

Bravo AF: 0.407

TwinsUK AF: 0.554 AC: 2053

ALSPAC AF: 0.548 AC: 2113

ESP6500AA AF: 0.176 AC: 774

ESP6500EA AF: 0.550 AC: 4733

ExAC AF: 0.501 AC: 60778

Asia WGS AF: 0.535 AC: 1863 AN: 3478

EpiCase AF: 0.563

EpiControl AF: 0.567

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	16
DANN	Benign	0.92
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.84	T
MetaRNN	Benign	0.000026	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.49	N
PhyloP100		1.4
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.058
Sift	Benign	0.069	T
Sift4G	Benign	0.15	T
Polyphen		0.054	B
Vest4		0.071
MPC		0.28
ClinPred		0.0067	T
GERP RS		3.6
Varity_R		0.31
gMVP		0.37
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1671036; hg19: chr17-73552185; COSMIC: COSV51344491; COSMIC: COSV51344491;