chr8-23337078-T-C

Position:

• chr8-23337078-T-C

Variant summary

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

The NM_002318.3(LOXL2):​c.744-3455A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 152,182 control chromosomes in the GnomAD database, including 2,220 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 0.16 (2220 hom., cov: 32)
  • Exomes 𝑓: 0.21 (0 hom.)
• Consequence: LOXL2 NM_002318.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.98

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]

LOXL2-AS1 (HGNC:56648): (LOXL2 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOXL2	NM_002318.3	c.744-3455A>G		intron_variant		ENST00000389131.8	NP_002309.1
LOXL2-AS1	NR_038323.1	n.871T>C		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LOXL2	ENST00000389131.8	c.744-3455A>G		intron_variant		1	NM_002318.3	ENSP00000373783	P1
LOXL2-AS1	ENST00000519692.1	n.871T>C		non_coding_transcript_exon_variant	1/3	1

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24906 AN: 152040 Hom.: 2219 Cov.: 32

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.0670

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.177

GnomAD4 exome AF: 0.208 AC: 5 AN: 24 Hom.: 0 Cov.: 0 AF XY: 0.250 AC XY: 5 AN XY: 20

Gnomad4 AFR exome AF: 0.00

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.188

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.164 AC: 24907 AN: 152158 Hom.: 2220 Cov.: 32 AF XY: 0.166 AC XY: 12384 AN XY: 74418

Gnomad4 AFR AF: 0.146

Gnomad4 AMR AF: 0.206

Gnomad4 ASJ AF: 0.145

Gnomad4 EAS AF: 0.0670

Gnomad4 SAS AF: 0.330

Gnomad4 FIN AF: 0.128

Gnomad4 NFE AF: 0.166

Gnomad4 OTH AF: 0.179

Alfa AF: 0.172 Hom.: 2232

Bravo AF: 0.161

Asia WGS AF: 0.201 AC: 699 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.30
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: rs883524; hg19: chr8-23194591;