rs2230472

Variant names:

• chr17-81906878-G-A
• rs2230472
• NM_002861.5:c.558C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_002861.5(PCYT2):​c.558C>T​(p.Pro186Pro) 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:3
• Conservation: PhyloP100: 0.547
• Publications: 0 publications found

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]

PCYT2 Gene-Disease associations (from GenCC):

• spastic paraplegia 82, autosomal recessive

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002861.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCYT2	NM_002861.5	MANE Select	c.558C>T	p.Pro186Pro	synonymous	Exon 7 of 13	NP_002852.1	Q99447-1
	PCYT2	NM_001184917.3		c.612C>T	p.Pro204Pro	synonymous	Exon 8 of 14	NP_001171846.1	Q99447-3
	PCYT2	NM_001330518.2		c.558C>T	p.Pro186Pro	synonymous	Exon 7 of 12	NP_001317447.1	I3L1R7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCYT2	ENST00000538936.7	TSL:1 MANE Select	c.558C>T	p.Pro186Pro	synonymous	Exon 7 of 13	ENSP00000439245.3	Q99447-1
	PCYT2	ENST00000538721.6	TSL:1	c.612C>T	p.Pro204Pro	synonymous	Exon 8 of 14	ENSP00000442050.2	Q99447-3
	PCYT2	ENST00000883690.1		c.714C>T	p.Pro238Pro	synonymous	Exon 9 of 15	ENSP00000553749.1

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

GnomAD2 exomes AF: 0.00516 AC: 1291 AN: 250418 AF XY: 0.00406

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 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

African (AFR) AF: 0.0739 AC: 2474 AN: 33478

American (AMR) AF: 0.00338 AC: 151 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00211 AC: 55 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000104 AC: 9 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52490

Middle Eastern (MID) AF: 0.00260 AC: 15 AN: 5764

European-Non Finnish (NFE) AF: 0.000126 AC: 140 AN: 1111910

Other (OTH) AF: 0.00429 AC: 259 AN: 60376

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

African (AFR) AF: 0.0692 AC: 2877 AN: 41554

American (AMR) AF: 0.00882 AC: 135 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00432 AC: 15 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68022

Other (OTH) AF: 0.00947 AC: 20 AN: 2112

Alfa AF: 0.00949 Hom.: 22

Bravo AF: 0.0219

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000237

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	8.8
DANN	Benign	0.87
PhyloP100		0.55
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.8
Mutation Taster		=99/1	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: rs2230472; hg19: chr17-79864754;