2-216043961-G-C

Position:

• chr2-216043961-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018441.6(PECR):​c.769C>G​(p.Gln257Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,638 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PECR NM_018441.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.02

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15246189).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PECR	NM_018441.6	c.769C>G	p.Gln257Glu	missense_variant	7/8	ENST00000265322.8	NP_060911.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PECR	ENST00000265322.8	c.769C>G	p.Gln257Glu	missense_variant	7/8	1	NM_018441.6	ENSP00000265322.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460638 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726748

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 25, 2024

The c.769C>G (p.Q257E) alteration is located in exon 7 (coding exon 7) of the PECR gene. This alteration results from a C to G substitution at nucleotide position 769, causing the glutamine (Q) at amino acid position 257 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.029	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	16
DANN	Benign	0.53
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.24
Eigen_PC	Benign	0.0071
FATHMM_MKL	Benign	0.72	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.56	T
MutationAssessor	Benign	0.32	N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.30	N
REVEL	Benign	0.25
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.079	B
Vest4		0.19
MutPred		0.53		Loss of sheet (P = 0.1158);
MVP		0.92
MPC		0.071
ClinPred		0.21	T
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.29
gMVP		0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1276575792; hg19: chr2-216908684;