8-23304470-T-C

Variant names:

• chr8-23304470-T-C
• rs3808524
• NM_002318.3:c.1881-1073A>G

Variant summary

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

The NM_002318.3(LOXL2):​c.1881-1073A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 151,772 control chromosomes in the GnomAD database, including 19,222 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 0.50 (19222 hom., cov: 32)
• Consequence: LOXL2 NM_002318.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90
• Publications: 4 publications found

Genes affected

LOXL2 (HGNC:6666): (lysyl oxidase like 2) This gene encodes a member of the lysyl oxidase gene family. The prototypic member of the family is essential to the biogenesis of connective tissue, encoding an extracellular copper-dependent amine oxidase that catalyses the first step in the formation of crosslinks in collagens and elastin. A highly conserved amino acid sequence at the C-terminus end appears to be sufficient for amine oxidase activity, suggesting that each family member may retain this function. The N-terminus is poorly conserved and may impart additional roles in developmental regulation, senescence, tumor suppression, cell growth control, and chemotaxis to each member of the family. [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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002318.3. 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
	LOXL2	NM_002318.3	MANE Select	c.1881-1073A>G		intron	N/A	NP_002309.1	Q9Y4K0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOXL2	ENST00000389131.8	TSL:1 MANE Select	c.1881-1073A>G		intron	N/A	ENSP00000373783.3	Q9Y4K0
	LOXL2	ENST00000879573.1		c.1899-1073A>G		intron	N/A	ENSP00000549632.1
	LOXL2	ENST00000879572.1		c.1881-1073A>G		intron	N/A	ENSP00000549631.1

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75436 AN: 151654 Hom.: 19212 Cov.: 32

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.602

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.839

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.514

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.502

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.497 AC: 75493 AN: 151772 Hom.: 19222 Cov.: 32 AF XY: 0.504 AC XY: 37345 AN XY: 74170

African (AFR) AF: 0.510 AC: 21083 AN: 41374

American (AMR) AF: 0.506 AC: 7719 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.493 AC: 1711 AN: 3468

East Asian (EAS) AF: 0.839 AC: 4321 AN: 5150

South Asian (SAS) AF: 0.537 AC: 2590 AN: 4822

European-Finnish (FIN) AF: 0.514 AC: 5408 AN: 10514

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.455 AC: 30914 AN: 67870

Other (OTH) AF: 0.505 AC: 1067 AN: 2112

Alfa AF: 0.479 Hom.: 3113

Bravo AF: 0.502

Asia WGS AF: 0.678 AC: 2357 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.0090
DANN	Benign	0.27
PhyloP100		-1.9
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: rs3808524; hg19: chr8-23161983;