Genetic Variant LOXL2:c.-83-67G>A (chr8-23368501-C-T) – 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.-83-67G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 651,272 control chromosomes in the GnomAD database, including 44,976 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 0.36 ( 9979 hom., cov: 32)

Exomes 𝑓: 0.37 ( 34997 hom. )

Consequence

LOXL2
NM_002318.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.92

Publications

11 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:

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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=-0.98).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOXL2	NM_002318.3 link	c.-83-67G>A		intron_variant	Intron 1 of 13	ENST00000389131.8	NP_002309.1	Q9Y4K0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LOXL2	ENST00000389131.8 link	c.-83-67G>A		intron_variant	Intron 1 of 13	1	NM_002318.3	ENSP00000373783.3		Q9Y4K0

Frequencies

GnomAD3 genomes

AF:

0.355

AC:

53939

AN:

151854

Hom.:

9971

Cov.:

show subpopulations

Gnomad AFR

AF:

0.297

Gnomad AMI

AF:

0.584

Gnomad AMR

AF:

0.429

Gnomad ASJ

AF:

0.343

Gnomad EAS

AF:

0.536

Gnomad SAS

AF:

0.306

Gnomad FIN

AF:

0.337

Gnomad MID

AF:

0.193

Gnomad NFE

AF:

0.365

Gnomad OTH

AF:

0.351

GnomAD4 exome

AF:

0.367

AC:

183446

AN:

499300

Hom.:

34997

AF XY:

0.364

AC XY:

95791

AN XY:

263394

show subpopulations

African (AFR)

AF:

0.288

AC:

4052

AN:

14054

American (AMR)

AF:

0.480

AC:

11803

AN:

24614

Ashkenazi Jewish (ASJ)

AF:

0.319

AC:

4837

AN:

15168

East Asian (EAS)

AF:

0.540

AC:

16983

AN:

31460

South Asian (SAS)

AF:

0.303

AC:

15213

AN:

50196

European-Finnish (FIN)

AF:

0.355

AC:

10753

AN:

30322

Middle Eastern (MID)

AF:

0.245

AC:

786

AN:

3202

European-Non Finnish (NFE)

AF:

0.361

AC:

109211

AN:

302276

Other (OTH)

AF:

0.350

AC:

9808

AN:

28008

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

6193

12385

18578

24770

30963

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

920

1840

2760

3680

4600

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.355

AC:

53980

AN:

151972

Hom.:

9979

Cov.:

AF XY:

0.355

AC XY:

26366

AN XY:

74270

show subpopulations

African (AFR)

AF:

0.297

AC:

12320

AN:

41442

American (AMR)

AF:

0.429

AC:

6554

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.343

AC:

1191

AN:

3468

East Asian (EAS)

AF:

0.536

AC:

2758

AN:

5146

South Asian (SAS)

AF:

0.307

AC:

1479

AN:

4824

European-Finnish (FIN)

AF:

0.337

AC:

3558

AN:

10560

Middle Eastern (MID)

AF:

0.187

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.365

AC:

24799

AN:

67944

Other (OTH)

AF:

0.348

AC:

735

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1765

3531

5296

7062

8827

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

534

1068

1602

2136

2670

<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:

0.358

Hom.:

41841

Bravo

AF:

0.365

Asia WGS

AF:

0.386

AC:

1343

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.022

(source)

DANN

Benign

0.73

PhyloP100

-2.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over