2-216058896-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_018441.6(PECR):c.505G>C(p.Val169Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000953 in 1,565,178 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0053 (13 hom., cov: 33)
  • Exomes 𝑓: 0.00049 (6 hom.)
• Consequence: PECR NM_018441.6 missense, splice_region
• Scores: Splicing: ADA: 0.0001241
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0690

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007910341).
• BP6: Variant 2-216058896-C-G is Benign according to our data. Variant chr2-216058896-C-G is described in ClinVar as [Benign]. Clinvar id is 790515.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00528 (804/152288) while in subpopulation AFR AF= 0.0185 (767/41544). AF 95% confidence interval is 0.0174. There are 13 homozygotes in gnomad4. There are 374 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PECR	NM_018441.6	c.505G>C	p.Val169Leu	missense_variant, splice_region_variant	4/8	ENST00000265322.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PECR	ENST00000265322.8	c.505G>C	p.Val169Leu	missense_variant, splice_region_variant	4/8	1	NM_018441.6	P1
PECR	ENST00000461330.5	n.386G>C		splice_region_variant, non_coding_transcript_exon_variant	3/7	2
PECR	ENST00000497889.5	n.509G>C		splice_region_variant, non_coding_transcript_exon_variant	4/7	5
PECR	ENST00000442122.5	c.424+6416G>C		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.00528 AC: 804 AN: 152170 Hom.: 13 Cov.: 33

Gnomad AFR AF: 0.0185

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00129 AC: 323 AN: 251232 Hom.: 3 AF XY: 0.000884 AC XY: 120 AN XY: 135778

Gnomad AFR exome AF: 0.0175

Gnomad AMR exome AF: 0.000897

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.000979

GnomAD4 exome AF: 0.000486 AC: 687 AN: 1412890 Hom.: 6 Cov.: 25 AF XY: 0.000415 AC XY: 293 AN XY: 706118

Gnomad4 AFR exome AF: 0.0174

Gnomad4 AMR exome AF: 0.000985

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000352

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000103

Gnomad4 OTH exome AF: 0.00109

GnomAD4 genome AF: 0.00528 AC: 804 AN: 152288 Hom.: 13 Cov.: 33 AF XY: 0.00502 AC XY: 374 AN XY: 74464

Gnomad4 AFR AF: 0.0185

Gnomad4 AMR AF: 0.00177

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.000300 Hom.: 0

Bravo AF: 0.00592

ESP6500AA AF: 0.0175 AC: 77

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00161 AC: 195

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 02, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.64
Cadd	Benign	5.7
Dann	Benign	0.96
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.82	T
MetaRNN	Benign	0.0079	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.77	N
REVEL	Benign	0.064
Sift	Uncertain	0.029	D
Sift4G	Uncertain	0.047	D
Polyphen		0.0	B
Vest4		0.12
MutPred		0.67		Loss of MoRF binding (P = 0.3539);
MVP		0.19
MPC		0.051
ClinPred		0.0057	T
GERP RS		0.058
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.21
gMVP		0.72

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00012
dbscSNV1_RF	Benign	0.056
SpliceAI score (max)		0.11		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs62001895; hg19: chr2-216923619; COSMIC: COSV99037037; COSMIC: COSV99037037;