8-76980884-T-C

Variant names:

• chr8-76980884-T-C
• rs4388434
• NM_000318.3:c.*2377A>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.*2377A>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 0.952 in 152,294 control chromosomes in the GnomAD database, including 69,148 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.95 (69146 hom., cov: 32)
  • Exomes 𝑓: 1.0 (2 hom.)
• Consequence: PEX2 NM_000318.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.600
• Publications: 3 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=-0.87).
• BP6: Variant 8-76980884-T-C is Benign according to our data. Variant chr8-76980884-T-C is described in ClinVar as Benign. ClinVar VariationId is 363777.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 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.*2377A>G		3_prime_UTR	Exon 4 of 4	NP_000309.2	P28328
	PEX2	NM_001079867.2		c.*2377A>G		3_prime_UTR	Exon 3 of 3	NP_001073336.2	P28328
	PEX2	NM_001172086.2		c.*2377A>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.*2377A>G		3_prime_UTR	Exon 4 of 4	ENSP00000349543.4	P28328

Frequencies

GnomAD3 genomes AF: 0.952 AC: 144870 AN: 152172 Hom.: 69106 Cov.: 32

Gnomad AFR AF: 0.887

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.982

Gnomad ASJ AF: 0.993

Gnomad EAS AF: 0.991

Gnomad SAS AF: 0.964

Gnomad FIN AF: 0.941

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.980

Gnomad OTH AF: 0.962

GnomAD4 exome AF: 1.00 AC: 4 AN: 4 Hom.: 2 Cov.: 0 AF XY: 1.00 AC XY: 4 AN XY: 4

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: 1.00 AC: 4 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.952 AC: 144965 AN: 152290 Hom.: 69146 Cov.: 32 AF XY: 0.951 AC XY: 70825 AN XY: 74464

African (AFR) AF: 0.887 AC: 36818 AN: 41530

American (AMR) AF: 0.982 AC: 15022 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.993 AC: 3446 AN: 3472

East Asian (EAS) AF: 0.991 AC: 5135 AN: 5182

South Asian (SAS) AF: 0.964 AC: 4661 AN: 4834

European-Finnish (FIN) AF: 0.941 AC: 9991 AN: 10616

Middle Eastern (MID) AF: 0.986 AC: 290 AN: 294

European-Non Finnish (NFE) AF: 0.980 AC: 66660 AN: 68036

Other (OTH) AF: 0.962 AC: 2030 AN: 2110

Alfa AF: 0.970 Hom.: 40685

Bravo AF: 0.954

Asia WGS AF: 0.979 AC: 3404 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	-0.87
CADD	Benign	1.0
DANN	Benign	0.42
PhyloP100		-0.60
Mutation Taster		=100/0	polymorphism (auto)

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: rs4388434; hg19: chr8-77893120;