8-23333428-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002318.3(LOXL2):c.939A>G(p.Ser313=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 1,613,396 control chromosomes in the GnomAD database, including 235,542 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 0.48 (18639 hom., cov: 32)
  • Exomes 𝑓: 0.54 (216903 hom.)
• Consequence: LOXL2 NM_002318.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.96

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP7: Synonymous conserved (PhyloP=-5.96 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOXL2	NM_002318.3	c.939A>G	p.Ser313=	synonymous_variant	5/14	ENST00000389131.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LOXL2	ENST00000389131.8	c.939A>G	p.Ser313=	synonymous_variant	5/14	1	NM_002318.3	P1

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73490 AN: 151876 Hom.: 18629 Cov.: 32

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.601

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.613

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.579

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.476

GnomAD3 exomes AF: 0.497 AC: 124981 AN: 251218 Hom.: 32244 AF XY: 0.501 AC XY: 68107 AN XY: 135844

Gnomad AFR exome AF: 0.337

Gnomad AMR exome AF: 0.371

Gnomad ASJ exome AF: 0.616

Gnomad EAS exome AF: 0.470

Gnomad SAS exome AF: 0.380

Gnomad FIN exome AF: 0.586

Gnomad NFE exome AF: 0.567

Gnomad OTH exome AF: 0.516

GnomAD4 exome AF: 0.540 AC: 789612 AN: 1461402 Hom.: 216903 Cov.: 57 AF XY: 0.538 AC XY: 391017 AN XY: 727010

Gnomad4 AFR exome AF: 0.336

Gnomad4 AMR exome AF: 0.375

Gnomad4 ASJ exome AF: 0.615

Gnomad4 EAS exome AF: 0.488

Gnomad4 SAS exome AF: 0.384

Gnomad4 FIN exome AF: 0.588

Gnomad4 NFE exome AF: 0.565

Gnomad4 OTH exome AF: 0.513

GnomAD4 genome AF: 0.484 AC: 73524 AN: 151994 Hom.: 18639 Cov.: 32 AF XY: 0.479 AC XY: 35571 AN XY: 74270

Gnomad4 AFR AF: 0.347

Gnomad4 AMR AF: 0.406

Gnomad4 ASJ AF: 0.613

Gnomad4 EAS AF: 0.466

Gnomad4 SAS AF: 0.382

Gnomad4 FIN AF: 0.579

Gnomad4 NFE AF: 0.571

Gnomad4 OTH AF: 0.474

Alfa AF: 0.547 Hom.: 33583

Bravo AF: 0.467

Asia WGS AF: 0.418 AC: 1454 AN: 3478

EpiCase AF: 0.553

EpiControl AF: 0.557

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.031
Dann	Benign	0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1010156; hg19: chr8-23190941; COSMIC: COSV66691569; COSMIC: COSV66691569;