8-23302642-C-T

Position:

• chr8-23302642-C-T

Variant summary

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

The NM_002318.3(LOXL2):​c.1997-479G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 152,178 control chromosomes in the GnomAD database, including 3,114 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 0.18 (3114 hom., cov: 33)
• Consequence: LOXL2 NM_002318.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.361

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOXL2	NM_002318.3	c.1997-479G>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.1997-479G>A		intron_variant		1	NM_002318.3	ENSP00000373783.3

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27279 AN: 152060 Hom.: 3116 Cov.: 33

Gnomad AFR AF: 0.0610

Gnomad AMI AF: 0.255

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.0839

Gnomad SAS AF: 0.0991

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.205

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

GnomAD4 genome AF: 0.179 AC: 27270 AN: 152178 Hom.: 3114 Cov.: 33 AF XY: 0.180 AC XY: 13416 AN XY: 74402

Gnomad4 AFR AF: 0.0608

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.254

Gnomad4 EAS AF: 0.0841

Gnomad4 SAS AF: 0.0996

Gnomad4 FIN AF: 0.274

Gnomad4 NFE AF: 0.244

Gnomad4 OTH AF: 0.202

Alfa AF: 0.232 Hom.: 7779

Bravo AF: 0.171

Asia WGS AF: 0.0850 AC: 298 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.22
DANN	Benign	0.73

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: rs17760913; hg19: chr8-23160155;