2-216039296-A-T

Variant names:

• chr2-216039296-A-T
• rs9288513
• NM_018441.6:c.891T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018441.6(PECR):​c.891T>A​(p.Phe297Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 1,600,236 control chromosomes in the GnomAD database, including 13,508 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.14 (1836 hom., cov: 33)
  • Exomes 𝑓: 0.12 (11672 hom.)
• Consequence: PECR NM_018441.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55
• Publications: 24 publications found

Genes affected

PECR (HGNC:18281): (peroxisomal trans-2-enoyl-CoA reductase) Enables signaling receptor binding activity and trans-2-enoyl-CoA reductase (NADPH) activity. Involved in phytol metabolic process. Located in peroxisome. [provided by Alliance of Genome Resources, Apr 2022]

PECR Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0044097602).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PECR	NM_018441.6	c.891T>A	p.Phe297Leu	missense_variant	Exon 8 of 8	ENST00000265322.8	NP_060911.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PECR	ENST00000265322.8	c.891T>A	p.Phe297Leu	missense_variant	Exon 8 of 8	1	NM_018441.6	ENSP00000265322.7
PECR	ENST00000442122.5	n.*335T>A		non_coding_transcript_exon_variant	Exon 7 of 8	2		ENSP00000395512.1
PECR	ENST00000461330.5	n.772T>A		non_coding_transcript_exon_variant	Exon 7 of 7	2
PECR	ENST00000442122.5	n.*335T>A		3_prime_UTR_variant	Exon 7 of 8	2		ENSP00000395512.1

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21168 AN: 152016 Hom.: 1829 Cov.: 33

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.0539

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.0659

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0946

Gnomad OTH AF: 0.119

GnomAD2 exomes AF: 0.129 AC: 32439 AN: 251424 AF XY: 0.129

Gnomad AFR exome AF: 0.230

Gnomad AMR exome AF: 0.137

Gnomad ASJ exome AF: 0.0616

Gnomad EAS exome AF: 0.198

Gnomad FIN exome AF: 0.0662

Gnomad NFE exome AF: 0.0946

Gnomad OTH exome AF: 0.109

GnomAD4 exome AF: 0.115 AC: 166673 AN: 1448102 Hom.: 11672 Cov.: 27 AF XY: 0.117 AC XY: 84721 AN XY: 721438

African (AFR) AF: 0.236 AC: 7810 AN: 33148

American (AMR) AF: 0.138 AC: 6156 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.0566 AC: 1473 AN: 26034

East Asian (EAS) AF: 0.262 AC: 10391 AN: 39596

South Asian (SAS) AF: 0.221 AC: 18952 AN: 85944

European-Finnish (FIN) AF: 0.0679 AC: 3624 AN: 53396

Middle Eastern (MID) AF: 0.0891 AC: 512 AN: 5744

European-Non Finnish (NFE) AF: 0.101 AC: 110669 AN: 1099606

Other (OTH) AF: 0.118 AC: 7086 AN: 59924

GnomAD4 genome AF: 0.139 AC: 21195 AN: 152134 Hom.: 1836 Cov.: 33 AF XY: 0.141 AC XY: 10500 AN XY: 74380

African (AFR) AF: 0.228 AC: 9449 AN: 41460

American (AMR) AF: 0.128 AC: 1960 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0539 AC: 187 AN: 3472

East Asian (EAS) AF: 0.199 AC: 1031 AN: 5176

South Asian (SAS) AF: 0.225 AC: 1083 AN: 4814

European-Finnish (FIN) AF: 0.0659 AC: 699 AN: 10610

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.0946 AC: 6433 AN: 68004

Other (OTH) AF: 0.118 AC: 250 AN: 2114

Alfa AF: 0.105 Hom.: 715

Bravo AF: 0.146

TwinsUK AF: 0.0949 AC: 352

ALSPAC AF: 0.101 AC: 388

ESP6500AA AF: 0.226 AC: 994

ESP6500EA AF: 0.100 AC: 861

ExAC AF: 0.132 AC: 15994

Asia WGS AF: 0.214 AC: 744 AN: 3478

EpiCase AF: 0.0876

EpiControl AF: 0.0872

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.64
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	0.010
DANN	Benign	0.31
DEOGEN2	Benign	0.023	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0092	N
LIST_S2	Benign	0.29	T
MetaRNN	Benign	0.0044	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.72	N
PhyloP100		-1.6
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.17
Sift	Benign	0.28	T
Sift4G	Benign	0.28	T
Polyphen		0.0010	B
Vest4		0.023
MutPred		0.10		Loss of methylation at K298 (P = 0.0337);
MPC		0.058
ClinPred		0.0041	T
GERP RS		-8.6
Varity_R		0.11
gMVP		0.33
Mutation Taster		=98/2	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: rs9288513; hg19: chr2-216904019; COSMIC: COSV54735888; COSMIC: COSV54735888;