dbSNP rs6985160: LOXL2:c.-83-147A>G (chr8-23368581-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.-83-147A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.69 in 579,314 control chromosomes in the GnomAD database, including 140,497 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 0.73 ( 41003 hom., cov: 33)

Exomes 𝑓: 0.68 ( 99494 hom. )

Consequence

LOXL2
NM_002318.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.813

Publications

4 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:

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=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.835 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.-83-147A>G		intron	N/A	NP_002309.1	Q9Y4K0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LOXL2	ENST00000389131.8	TSL:1 MANE Select	c.-83-147A>G	intron	N/A	ENSP00000373783.3	Q9Y4K0
LOXL2	ENST00000879573.1		c.-83-147A>G	intron	N/A	ENSP00000549632.1
LOXL2	ENST00000879572.1		c.-83-147A>G	intron	N/A	ENSP00000549631.1

Frequencies

GnomAD3 genomes

AF:

0.727

AC:

110621

AN:

152086

Hom.:

40939

Cov.:

show subpopulations

Gnomad AFR

AF:

0.843

Gnomad AMI

AF:

0.714

Gnomad AMR

AF:

0.762

Gnomad ASJ

AF:

0.637

Gnomad EAS

AF:

0.847

Gnomad SAS

AF:

0.574

Gnomad FIN

AF:

0.720

Gnomad MID

AF:

0.481

Gnomad NFE

AF:

0.659

Gnomad OTH

AF:

0.717

GnomAD4 exome

AF:

0.677

AC:

289013

AN:

427110

Hom.:

99494

AF XY:

0.669

AC XY:

150350

AN XY:

224730

show subpopulations

African (AFR)

AF:

0.837

AC:

10135

AN:

12104

American (AMR)

AF:

0.794

AC:

14483

AN:

18234

Ashkenazi Jewish (ASJ)

AF:

0.617

AC:

8172

AN:

13242

East Asian (EAS)

AF:

0.874

AC:

25558

AN:

29258

South Asian (SAS)

AF:

0.570

AC:

25208

AN:

44226

European-Finnish (FIN)

AF:

0.723

AC:

19639

AN:

27176

Middle Eastern (MID)

AF:

0.613

AC:

1146

AN:

1870

European-Non Finnish (NFE)

AF:

0.655

AC:

167893

AN:

256220

Other (OTH)

AF:

0.677

AC:

16779

AN:

24780

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

4341

8683

13024

17366

21707

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

808

1616

2424

3232

4040

<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:

0.728

AC:

110744

AN:

152204

Hom.:

41003

Cov.:

AF XY:

0.730

AC XY:

54281

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.843

AC:

35000

AN:

41532

American (AMR)

AF:

0.762

AC:

11654

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.637

AC:

2213

AN:

3472

East Asian (EAS)

AF:

0.847

AC:

4375

AN:

5166

South Asian (SAS)

AF:

0.574

AC:

2768

AN:

4824

European-Finnish (FIN)

AF:

0.720

AC:

7627

AN:

10596

Middle Eastern (MID)

AF:

0.486

AC:

143

AN:

294

European-Non Finnish (NFE)

AF:

0.659

AC:

44794

AN:

67998

Other (OTH)

AF:

0.719

AC:

1519

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1531

3062

4593

6124

7655

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

830

1660

2490

3320

4150

<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:

0.683

Hom.:

7257

Bravo

AF:

0.742

Asia WGS

AF:

0.685

AC:

2382

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.88

(source)

DANN

Benign

0.33

PhyloP100

-0.81

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over