NM_002318.3:c.1996+362C>T

Variant names:

• chr8-23302920-G-A
• rs17760943
• NM_002318.3:c.1996+362C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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=-0.81).
• 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 rank	MANE	Protein	UniProt
LOXL2	NM_002318.3	c.1996+362C>T		intron_variant	Intron 11 of 13	ENST00000389131.8	NP_002309.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LOXL2	ENST00000389131.8	c.1996+362C>T		intron_variant	Intron 11 of 13	1	NM_002318.3	ENSP00000373783.3

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

African (AFR) AF: 0.0652 AC: 2708 AN: 41524

American (AMR) AF: 0.188 AC: 2879 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 920 AN: 3470

East Asian (EAS) AF: 0.0934 AC: 481 AN: 5148

South Asian (SAS) AF: 0.103 AC: 495 AN: 4824

European-Finnish (FIN) AF: 0.327 AC: 3462 AN: 10574

Middle Eastern (MID) AF: 0.288 AC: 84 AN: 292

European-Non Finnish (NFE) AF: 0.270 AC: 18386 AN: 67976

Other (OTH) AF: 0.212 AC: 448 AN: 2112

Alfa AF: 0.251 Hom.: 11109

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
PhyloP100		2.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17760943; hg19: chr8-23160433;