chr17-75543550-A-G

Variant names:

• chr17-75543550-A-G
• rs6501822
• NM_001031803.2:c.75+49A>G

Variant summary

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

The NM_001031803.2(LLGL2):​c.75+49A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.887 in 1,532,964 control chromosomes in the GnomAD database, including 607,727 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.85 (55151 hom., cov: 32)
  • Exomes 𝑓: 0.89 (552576 hom.)
• Consequence: LLGL2 NM_001031803.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.154
• Publications: 18 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 (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.907 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.75+49A>G		intron	N/A	NP_001026973.1	Q6P1M3-1
	LLGL2	NM_004524.3		c.75+49A>G		intron	N/A	NP_004515.2	Q6P1M3-2
	LLGL2	NM_001015002.2		c.75+49A>G		intron	N/A	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.75+49A>G		intron	N/A	ENSP00000376333.4	Q6P1M3-1
	LLGL2	ENST00000577200.5	TSL:1	c.75+49A>G		intron	N/A	ENSP00000464397.1	J3QRV5
	LLGL2	ENST00000167462.9	TSL:1	c.75+49A>G		intron	N/A	ENSP00000167462.5	Q6P1M3-2

Frequencies

GnomAD3 genomes AF: 0.848 AC: 128886 AN: 152044 Hom.: 55103 Cov.: 32

Gnomad AFR AF: 0.779

Gnomad AMI AF: 0.941

Gnomad AMR AF: 0.745

Gnomad ASJ AF: 0.846

Gnomad EAS AF: 0.679

Gnomad SAS AF: 0.871

Gnomad FIN AF: 0.907

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.913

Gnomad OTH AF: 0.849

GnomAD2 exomes AF: 0.836 AC: 190310 AN: 227662 AF XY: 0.852

Gnomad AFR exome AF: 0.775

Gnomad AMR exome AF: 0.595

Gnomad ASJ exome AF: 0.835

Gnomad EAS exome AF: 0.665

Gnomad FIN exome AF: 0.907

Gnomad NFE exome AF: 0.915

Gnomad OTH exome AF: 0.867

GnomAD4 exome AF: 0.891 AC: 1230969 AN: 1380802 Hom.: 552576 Cov.: 18 AF XY: 0.893 AC XY: 614997 AN XY: 688458

African (AFR) AF: 0.776 AC: 24476 AN: 31534

American (AMR) AF: 0.615 AC: 25400 AN: 41326

Ashkenazi Jewish (ASJ) AF: 0.839 AC: 20511 AN: 24436

East Asian (EAS) AF: 0.648 AC: 24828 AN: 38324

South Asian (SAS) AF: 0.885 AC: 71548 AN: 80878

European-Finnish (FIN) AF: 0.908 AC: 47522 AN: 52358

Middle Eastern (MID) AF: 0.922 AC: 5108 AN: 5540

European-Non Finnish (NFE) AF: 0.916 AC: 961340 AN: 1049026

Other (OTH) AF: 0.875 AC: 50236 AN: 57380

GnomAD4 genome AF: 0.848 AC: 128992 AN: 152162 Hom.: 55151 Cov.: 32 AF XY: 0.846 AC XY: 62960 AN XY: 74398

African (AFR) AF: 0.779 AC: 32331 AN: 41480

American (AMR) AF: 0.745 AC: 11387 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.846 AC: 2935 AN: 3470

East Asian (EAS) AF: 0.679 AC: 3516 AN: 5176

South Asian (SAS) AF: 0.871 AC: 4205 AN: 4826

European-Finnish (FIN) AF: 0.907 AC: 9613 AN: 10598

Middle Eastern (MID) AF: 0.922 AC: 271 AN: 294

European-Non Finnish (NFE) AF: 0.913 AC: 62089 AN: 68020

Other (OTH) AF: 0.850 AC: 1791 AN: 2108

Alfa AF: 0.882 Hom.: 166016

Bravo AF: 0.826

Asia WGS AF: 0.807 AC: 2806 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.52
DANN	Benign	0.21
PhyloP100		0.15
PromoterAI		-0.0032	Neutral
Mutation Taster		=100/0	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: rs6501822; hg19: chr17-73539631; COSMIC: COSV51344478; COSMIC: COSV51344478;