rs2230472

chr17-81906878-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_002861.5(PCYT2):c.558C>T(p.Pro186=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00383 in 1,613,116 control chromosomes in the GnomAD database, including 199 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.020 (102 hom., cov: 33)
  • Exomes 𝑓: 0.0021 (97 hom.)
• Consequence: PCYT2 NM_002861.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.547

Genes affected

PCYT2 (HGNC:8756): (phosphate cytidylyltransferase 2, ethanolamine) This gene encodes an enzyme that catalyzes the formation of CDP-ethanolamine from CTP and phosphoethanolamine in the Kennedy pathway of phospholipid synthesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 17-81906878-G-A is Benign according to our data. Variant chr17-81906878-G-A is described in ClinVar as [Benign]. Clinvar id is 777258.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.547 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCYT2	NM_002861.5	c.558C>T	p.Pro186=	synonymous_variant	7/13	ENST00000538936.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCYT2	ENST00000538936.7	c.558C>T	p.Pro186=	synonymous_variant	7/13	1	NM_002861.5	P1

Frequencies

GnomAD3 genomes AF: 0.0201 AC: 3063 AN: 152204 Hom.: 101 Cov.: 33

Gnomad AFR AF: 0.0693

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00883

Gnomad ASJ AF: 0.00432

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.00957

GnomAD3 exomes AF: 0.00516 AC: 1291 AN: 250418 Hom.: 42 AF XY: 0.00406 AC XY: 550 AN XY: 135610

Gnomad AFR exome AF: 0.0700

Gnomad AMR exome AF: 0.00281

Gnomad ASJ exome AF: 0.00270

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000204

Gnomad OTH exome AF: 0.00164

GnomAD4 exome AF: 0.00212 AC: 3103 AN: 1460794 Hom.: 97 Cov.: 33 AF XY: 0.00183 AC XY: 1333 AN XY: 726702

Gnomad4 AFR exome AF: 0.0739

Gnomad4 AMR exome AF: 0.00338

Gnomad4 ASJ exome AF: 0.00211

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000104

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000126

Gnomad4 OTH exome AF: 0.00429

GnomAD4 genome AF: 0.0201 AC: 3069 AN: 152322 Hom.: 102 Cov.: 33 AF XY: 0.0195 AC XY: 1454 AN XY: 74490

Gnomad4 AFR AF: 0.0692

Gnomad4 AMR AF: 0.00882

Gnomad4 ASJ AF: 0.00432

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000235

Gnomad4 OTH AF: 0.00947

Alfa AF: 0.00964 Hom.: 18

Bravo AF: 0.0219

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 06, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Aug 20, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
Cadd	Benign	8.8
Dann	Benign	0.87
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.8

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

Publications

LitVar

Other links and lift over

dbSNP: rs2230472; hg19: chr17-79864754;