8-76981119-T-C

Variant names:

• chr8-76981119-T-C
• rs79700176
• NM_000318.3:c.*2142A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000318.3(PEX2):​c.*2142A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0335 in 152,322 control chromosomes in the GnomAD database, including 103 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.034 (103 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PEX2 NM_000318.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.04
• Publications: 2 publications found

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]

PEX2 Gene-Disease associations (from GenCC):

• peroxisome biogenesis disorder

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• peroxisome biogenesis disorder 5A (Zellweger)

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P, Myriad Women’s Health
• peroxisome biogenesis disorder 5B

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• Zellweger spectrum disorders

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 8-76981119-T-C is Benign according to our data. Variant chr8-76981119-T-C is described in ClinVar as Benign. ClinVar VariationId is 363781.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0631 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000318.3. 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
	PEX2	NM_000318.3	MANE Select	c.*2142A>G		3_prime_UTR	Exon 4 of 4	NP_000309.2	P28328
	PEX2	NM_001079867.2		c.*2142A>G		3_prime_UTR	Exon 3 of 3	NP_001073336.2	P28328
	PEX2	NM_001172086.2		c.*2142A>G		3_prime_UTR	Exon 5 of 5	NP_001165557.2	P28328

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEX2	ENST00000357039.9	TSL:1 MANE Select	c.*2142A>G		3_prime_UTR	Exon 4 of 4	ENSP00000349543.4	P28328

Frequencies

GnomAD3 genomes AF: 0.0335 AC: 5094 AN: 152204 Hom.: 103 Cov.: 32

Gnomad AFR AF: 0.0649

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0231

Gnomad ASJ AF: 0.0161

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0345

Gnomad FIN AF: 0.0270

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0207

Gnomad OTH AF: 0.0387

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0335 AC: 5109 AN: 152322 Hom.: 103 Cov.: 32 AF XY: 0.0332 AC XY: 2469 AN XY: 74478

African (AFR) AF: 0.0651 AC: 2708 AN: 41572

American (AMR) AF: 0.0231 AC: 353 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0161 AC: 56 AN: 3470

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5182

South Asian (SAS) AF: 0.0346 AC: 167 AN: 4832

European-Finnish (FIN) AF: 0.0270 AC: 287 AN: 10624

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0207 AC: 1407 AN: 68022

Other (OTH) AF: 0.0383 AC: 81 AN: 2114

Alfa AF: 0.0309 Hom.: 41

Bravo AF: 0.0337

Asia WGS AF: 0.0440 AC: 152 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Peroxisome biogenesis disorder 5A (Zellweger) (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.48
DANN	Benign	0.67
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs79700176; hg19: chr8-77893355;