rs17760943

Positions:

• chr8-23302920-G-A

Variant summary

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

The NM_002318.3(LOXL2):​c.1996+362C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 152,122 control chromosomes in the GnomAD database, including 3,830 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 0.20 (3830 hom., cov: 31)
• Consequence: LOXL2 NM_002318.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.19

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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOXL2	NM_002318.3	c.1996+362C>T		intron_variant		ENST00000389131.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LOXL2	ENST00000389131.8	c.1996+362C>T		intron_variant		1	NM_002318.3	P1

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30144 AN: 152004 Hom.: 3832 Cov.: 31

Gnomad AFR AF: 0.0654

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.0932

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.287

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.215

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

GnomAD4 genome AF: 0.198 AC: 30135 AN: 152122 Hom.: 3830 Cov.: 31 AF XY: 0.201 AC XY: 14947 AN XY: 74338

Gnomad4 AFR AF: 0.0652

Gnomad4 AMR AF: 0.188

Gnomad4 ASJ AF: 0.265

Gnomad4 EAS AF: 0.0934

Gnomad4 SAS AF: 0.103

Gnomad4 FIN AF: 0.327

Gnomad4 NFE AF: 0.270

Gnomad4 OTH AF: 0.212

Alfa AF: 0.256 Hom.: 9529

Bravo AF: 0.186

Asia WGS AF: 0.0990 AC: 346 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.4
DANN	Benign	0.60

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: rs17760943; hg19: chr8-23160433;