2-216058956-C-T

Variant names:

• chr2-216058956-C-T
• rs1429148
• NM_018441.6:c.445G>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.445G>A​(p.Glu149Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.085 in 1,606,824 control chromosomes in the GnomAD database, including 9,161 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 0.12 (1528 hom., cov: 32)
  • Exomes 𝑓: 0.082 (7633 hom.)
• Consequence: PECR NM_018441.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.306
• Publications: 20 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=0.0012511313).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PECR	NM_018441.6	c.445G>A	p.Glu149Lys	missense_variant	Exon 4 of 8	ENST00000265322.8	NP_060911.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PECR	ENST00000265322.8	c.445G>A	p.Glu149Lys	missense_variant	Exon 4 of 8	1	NM_018441.6	ENSP00000265322.7
PECR	ENST00000461330.5	n.326G>A		non_coding_transcript_exon_variant	Exon 3 of 7	2
PECR	ENST00000497889.5	n.449G>A		non_coding_transcript_exon_variant	Exon 4 of 7	5
PECR	ENST00000442122.5	n.424+6356G>A		intron_variant	Intron 3 of 7	2		ENSP00000395512.1

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17776 AN: 152068 Hom.: 1521 Cov.: 32

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.0446

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.0309

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0572

Gnomad OTH AF: 0.101

GnomAD2 exomes AF: 0.108 AC: 27083 AN: 251176 AF XY: 0.108

Gnomad AFR exome AF: 0.226

Gnomad AMR exome AF: 0.134

Gnomad ASJ exome AF: 0.0479

Gnomad EAS exome AF: 0.201

Gnomad FIN exome AF: 0.0304

Gnomad NFE exome AF: 0.0583

Gnomad OTH exome AF: 0.0841

GnomAD4 exome AF: 0.0817 AC: 118836 AN: 1454638 Hom.: 7633 Cov.: 28 AF XY: 0.0849 AC XY: 61506 AN XY: 724168

African (AFR) AF: 0.233 AC: 7752 AN: 33208

American (AMR) AF: 0.133 AC: 5943 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.0447 AC: 1167 AN: 26092

East Asian (EAS) AF: 0.264 AC: 10456 AN: 39598

South Asian (SAS) AF: 0.217 AC: 18622 AN: 85958

European-Finnish (FIN) AF: 0.0326 AC: 1743 AN: 53408

Middle Eastern (MID) AF: 0.0812 AC: 467 AN: 5750

European-Non Finnish (NFE) AF: 0.0607 AC: 67104 AN: 1105770

Other (OTH) AF: 0.0928 AC: 5582 AN: 60148

GnomAD4 genome AF: 0.117 AC: 17799 AN: 152186 Hom.: 1528 Cov.: 32 AF XY: 0.119 AC XY: 8872 AN XY: 74414

African (AFR) AF: 0.223 AC: 9233 AN: 41488

American (AMR) AF: 0.116 AC: 1774 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0446 AC: 155 AN: 3472

East Asian (EAS) AF: 0.205 AC: 1060 AN: 5176

South Asian (SAS) AF: 0.223 AC: 1075 AN: 4826

European-Finnish (FIN) AF: 0.0309 AC: 328 AN: 10612

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0572 AC: 3893 AN: 68008

Other (OTH) AF: 0.101 AC: 213 AN: 2114

Alfa AF: 0.0810 Hom.: 3700

Bravo AF: 0.127

TwinsUK AF: 0.0531 AC: 197

ALSPAC AF: 0.0597 AC: 230

ESP6500AA AF: 0.214 AC: 941

ESP6500EA AF: 0.0591 AC: 508

ExAC AF: 0.110 AC: 13379

Asia WGS AF: 0.218 AC: 759 AN: 3478

EpiCase AF: 0.0579

EpiControl AF: 0.0565

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.8
DANN	Benign	0.86
DEOGEN2	Benign	0.12	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.85	T
MetaRNN	Benign	0.0013	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.53	N
PhyloP100		-0.31
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.036
Sift	Benign	0.64	T
Sift4G	Benign	0.43	T
Polyphen		0.0050	B
Vest4		0.030
MPC		0.058
ClinPred		0.0030	T
GERP RS		-1.0
Varity_R		0.28
gMVP		0.67
Mutation Taster		=91/9	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs1429148; hg19: chr2-216923679; COSMIC: COSV54736005; COSMIC: COSV54736005;