rs61752127

Variant names:

• chr8-76983510-C-A
• NM_000318.3:c.669G>T

Your query was ambiguous. Multiple possible variants found:

• chr8-76983510-C-A
• chr8-76983510-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000318.3(PEX2):​c.669G>T​(p.Trp223Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,736 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PEX2 NM_000318.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.15

Genes affected

PEX2 (HGNC:9717): (peroxisomal biogenesis factor 2) This gene encodes an integral peroxisomal membrane protein required for peroxisome biogenesis. The protein is thought to be involved in peroxisomal matrix protein import. Mutations in this gene result in one form of Zellweger syndrome and infantile Refsum disease. Alternative splicing results in multiple transcript variants encoding the same protein. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PEX2	NM_000318.3	c.669G>T	p.Trp223Cys	missense_variant	Exon 4 of 4	ENST00000357039.9	NP_000309.2
PEX2	NM_001079867.2	c.669G>T	p.Trp223Cys	missense_variant	Exon 3 of 3		NP_001073336.2
PEX2	NM_001172086.2	c.669G>T	p.Trp223Cys	missense_variant	Exon 5 of 5		NP_001165557.2
PEX2	NM_001172087.2	c.669G>T	p.Trp223Cys	missense_variant	Exon 3 of 3		NP_001165558.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PEX2	ENST00000357039.9	c.669G>T	p.Trp223Cys	missense_variant	Exon 4 of 4	1	NM_000318.3	ENSP00000349543.4
PEX2	ENST00000522527.5	c.669G>T	p.Trp223Cys	missense_variant	Exon 3 of 3	1		ENSP00000428638.1
PEX2	ENST00000520103.5	c.669G>T	p.Trp223Cys	missense_variant	Exon 3 of 3	2		ENSP00000428590.1
PEX2	ENST00000518986.5	c.*130G>T		downstream_gene_variant		3		ENSP00000429304.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461736 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727174

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.77	D;D;D
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.77	.;.;T
M_CAP	Benign	0.0098	T
MetaRNN	Uncertain	0.52	D;D;D
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.0	M;M;M
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-2.4	N;N;N
REVEL	Uncertain	0.36
Sift	Benign	0.050	D;D;D
Sift4G	Uncertain	0.043	D;D;D
Polyphen		0.99	D;D;D
Vest4		0.27
MutPred		0.76		Loss of catalytic residue at P226 (P = 0.0291);Loss of catalytic residue at P226 (P = 0.0291);Loss of catalytic residue at P226 (P = 0.0291);
MVP		0.82
ClinPred		0.92	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.51
gMVP		0.88

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-77895746;