rs3808522

chr8-23304663-T-Cchr8-23304663-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002318.3(LOXL2):c.1881-1266A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 152,014 control chromosomes in the GnomAD database, including 20,168 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 0.51 (20168 hom., cov: 32)
• Consequence: LOXL2 NM_002318.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.30

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.817 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOXL2	NM_002318.3	c.1881-1266A>G		intron_variant		ENST00000389131.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LOXL2	ENST00000389131.8	c.1881-1266A>G		intron_variant		1	NM_002318.3	P1

Frequencies

GnomAD3 genomes AF: 0.508 AC: 77186 AN: 151896 Hom.: 20153 Cov.: 32

Gnomad AFR AF: 0.546

Gnomad AMI AF: 0.606

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.494

Gnomad EAS AF: 0.838

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.518

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.507

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

GnomAD4 genome AF: 0.508 AC: 77249 AN: 152014 Hom.: 20168 Cov.: 32 AF XY: 0.514 AC XY: 38194 AN XY: 74286

Gnomad4 AFR AF: 0.546

Gnomad4 AMR AF: 0.509

Gnomad4 ASJ AF: 0.494

Gnomad4 EAS AF: 0.838

Gnomad4 SAS AF: 0.537

Gnomad4 FIN AF: 0.518

Gnomad4 NFE AF: 0.456

Gnomad4 OTH AF: 0.510

Alfa AF: 0.469 Hom.: 29947

Bravo AF: 0.512

Asia WGS AF: 0.679 AC: 2359 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.011
Dann	Benign	0.24

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

Publications

LitVar

Other links and lift over

dbSNP: rs3808522; hg19: chr8-23162176;