8-23368501-C-T

Position:

• chr8-23368501-C-T

Variant summary

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

The ENST00000389131.8(LOXL2):​c.-83-67G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 651,272 control chromosomes in the GnomAD database, including 44,976 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 0.36 (9979 hom., cov: 32)
  • Exomes 𝑓: 0.37 (34997 hom.)
• Consequence: LOXL2 ENST00000389131.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.92

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOXL2	NM_002318.3	c.-83-67G>A		intron_variant		ENST00000389131.8	NP_002309.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LOXL2	ENST00000389131.8	c.-83-67G>A		intron_variant		1	NM_002318.3	ENSP00000373783	P1

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53939 AN: 151854 Hom.: 9971 Cov.: 32

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.584

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.536

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.351

GnomAD4 exome AF: 0.367 AC: 183446 AN: 499300 Hom.: 34997 AF XY: 0.364 AC XY: 95791 AN XY: 263394

Gnomad4 AFR exome AF: 0.288

Gnomad4 AMR exome AF: 0.480

Gnomad4 ASJ exome AF: 0.319

Gnomad4 EAS exome AF: 0.540

Gnomad4 SAS exome AF: 0.303

Gnomad4 FIN exome AF: 0.355

Gnomad4 NFE exome AF: 0.361

Gnomad4 OTH exome AF: 0.350

GnomAD4 genome AF: 0.355 AC: 53980 AN: 151972 Hom.: 9979 Cov.: 32 AF XY: 0.355 AC XY: 26366 AN XY: 74270

Gnomad4 AFR AF: 0.297

Gnomad4 AMR AF: 0.429

Gnomad4 ASJ AF: 0.343

Gnomad4 EAS AF: 0.536

Gnomad4 SAS AF: 0.307

Gnomad4 FIN AF: 0.337

Gnomad4 NFE AF: 0.365

Gnomad4 OTH AF: 0.348

Alfa AF: 0.353 Hom.: 19793

Bravo AF: 0.365

Asia WGS AF: 0.386 AC: 1343 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.022
DANN	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6999447; hg19: chr8-23226014;