8-23333428-T-C

Variant names:

• chr8-23333428-T-C
• rs1010156
• NM_002318.3:c.939A>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_002318.3(LOXL2):​c.939A>G​(p.Ser313Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 1,613,396 control chromosomes in the GnomAD database, including 235,542 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 0.48 (18639 hom., cov: 32)
  • Exomes 𝑓: 0.54 (216903 hom.)
• Consequence: LOXL2 NM_002318.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.96
• Publications: 22 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.04).
• BP7: Synonymous conserved (PhyloP=-5.96 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.566 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.939A>G	p.Ser313Ser	synonymous	Exon 5 of 14	NP_002309.1	Q9Y4K0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOXL2	ENST00000389131.8	TSL:1 MANE Select	c.939A>G	p.Ser313Ser	synonymous	Exon 5 of 14	ENSP00000373783.3	Q9Y4K0
	LOXL2	ENST00000879573.1		c.939A>G	p.Ser313Ser	synonymous	Exon 5 of 14	ENSP00000549632.1
	LOXL2	ENST00000879572.1		c.939A>G	p.Ser313Ser	synonymous	Exon 6 of 15	ENSP00000549631.1

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73490 AN: 151876 Hom.: 18629 Cov.: 32

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.601

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.613

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.579

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.476

GnomAD2 exomes AF: 0.497 AC: 124981 AN: 251218 AF XY: 0.501

Gnomad AFR exome AF: 0.337

Gnomad AMR exome AF: 0.371

Gnomad ASJ exome AF: 0.616

Gnomad EAS exome AF: 0.470

Gnomad FIN exome AF: 0.586

Gnomad NFE exome AF: 0.567

Gnomad OTH exome AF: 0.516

GnomAD4 exome AF: 0.540 AC: 789612 AN: 1461402 Hom.: 216903 Cov.: 57 AF XY: 0.538 AC XY: 391017 AN XY: 727010

African (AFR) AF: 0.336 AC: 11251 AN: 33474

American (AMR) AF: 0.375 AC: 16781 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.615 AC: 16064 AN: 26134

East Asian (EAS) AF: 0.488 AC: 19363 AN: 39688

South Asian (SAS) AF: 0.384 AC: 33087 AN: 86250

European-Finnish (FIN) AF: 0.588 AC: 31202 AN: 53040

Middle Eastern (MID) AF: 0.464 AC: 2674 AN: 5768

European-Non Finnish (NFE) AF: 0.565 AC: 628185 AN: 1111934

Other (OTH) AF: 0.513 AC: 31005 AN: 60392

GnomAD4 genome AF: 0.484 AC: 73524 AN: 151994 Hom.: 18639 Cov.: 32 AF XY: 0.479 AC XY: 35571 AN XY: 74270

African (AFR) AF: 0.347 AC: 14364 AN: 41446

American (AMR) AF: 0.406 AC: 6197 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.613 AC: 2126 AN: 3470

East Asian (EAS) AF: 0.466 AC: 2404 AN: 5158

South Asian (SAS) AF: 0.382 AC: 1839 AN: 4818

European-Finnish (FIN) AF: 0.579 AC: 6107 AN: 10546

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.571 AC: 38793 AN: 67966

Other (OTH) AF: 0.474 AC: 1001 AN: 2114

Alfa AF: 0.538 Hom.: 80662

Bravo AF: 0.467

Asia WGS AF: 0.418 AC: 1454 AN: 3478

EpiCase AF: 0.553

EpiControl AF: 0.557

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.031
DANN	Benign	0.51
PhyloP100		-6.0
PromoterAI		0.013	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1010156; hg19: chr8-23190941; COSMIC: COSV66691569; COSMIC: COSV66691569;