NM_002318.3:c.1997-479G>A

Variant names:

• chr8-23302642-C-T
• rs17760913
• NM_002318.3:c.1997-479G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002318.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOXL2	NM_002318.3	MANE Select	c.1997-479G>A		intron	N/A	NP_002309.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOXL2	ENST00000389131.8	TSL:1 MANE Select	c.1997-479G>A		intron	N/A	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

African (AFR) AF: 0.0608 AC: 2525 AN: 41512

American (AMR) AF: 0.179 AC: 2744 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 882 AN: 3468

East Asian (EAS) AF: 0.0841 AC: 436 AN: 5186

South Asian (SAS) AF: 0.0996 AC: 480 AN: 4818

European-Finnish (FIN) AF: 0.274 AC: 2904 AN: 10598

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.244 AC: 16562 AN: 67990

Other (OTH) AF: 0.202 AC: 427 AN: 2114

Alfa AF: 0.218 Hom.: 9535

Bravo AF: 0.171

Asia WGS AF: 0.0850 AC: 298 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.22
DANN	Benign	0.73
PhyloP100		-0.36
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17760913; hg19: chr8-23160155;