dbSNP rs883524: LOXL2:c.744-3455A>G (chr8-23337078-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.98

Publications

6 publications found

Variant links:

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 links:

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

LOXL2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOXL2	NM_002318.3	MANE Select	c.744-3455A>G		intron	N/A	NP_002309.1	Q9Y4K0
	LOXL2-AS1	NR_038323.1		n.871T>C		non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LOXL2	ENST00000389131.8	TSL:1 MANE Select	c.744-3455A>G	intron	N/A	ENSP00000373783.3	Q9Y4K0
LOXL2-AS1	ENST00000519692.1	TSL:1	n.871T>C	non_coding_transcript_exon	Exon 1 of 3
LOXL2	ENST00000879573.1		c.744-3455A>G	intron	N/A	ENSP00000549632.1

Frequencies

GnomAD3 genomes

AF:

0.164

AC:

24906

AN:

152040

Hom.:

2219

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AF XY:

0.250

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.250

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.188

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.164

AC:

24907

AN:

152158

Hom.:

2220

Cov.:

AF XY:

0.166

AC XY:

12384

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.146

AC:

6065

AN:

41498

American (AMR)

AF:

0.206

AC:

3156

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.145

AC:

504

AN:

3466

East Asian (EAS)

AF:

0.0670

AC:

347

AN:

5180

South Asian (SAS)

AF:

0.330

AC:

1591

AN:

4822

European-Finnish (FIN)

AF:

0.128

AC:

1357

AN:

10598

Middle Eastern (MID)

AF:

0.240

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.166

AC:

11288

AN:

67992

Other (OTH)

AF:

0.179

AC:

377

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1062

2125

3187

4250

5312

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

280

560

840

1120

1400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.171

Hom.:

3269

Bravo

AF:

0.161

Asia WGS

AF:

0.201

AC:

699

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.30

(source)

DANN

Benign

0.73

PhyloP100

-2.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over