17-81904754-G-A

Variant names:

• chr17-81904754-G-A
• rs7405872
• NM_002861.5:c.*79C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002861.5(PCYT2):​c.*79C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0509 in 906,608 control chromosomes in the GnomAD database, including 1,418 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.040 (160 hom., cov: 33)
  • Exomes 𝑓: 0.053 (1258 hom.)
• Consequence: PCYT2 NM_002861.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.957
• Publications: 2 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 17-81904754-G-A is Benign according to our data. Variant chr17-81904754-G-A is described in ClinVar as Benign. ClinVar VariationId is 1268709.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0905 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.*79C>T		3_prime_UTR	Exon 13 of 13	NP_002852.1	Q99447-1
	PCYT2	NM_001184917.3		c.*79C>T		3_prime_UTR	Exon 14 of 14	NP_001171846.1	Q99447-3
	PCYT2	NM_001330518.2		c.*79C>T		3_prime_UTR	Exon 12 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.*79C>T		3_prime_UTR	Exon 13 of 13	ENSP00000439245.3	Q99447-1
	PCYT2	ENST00000538721.6	TSL:1	c.*79C>T		3_prime_UTR	Exon 14 of 14	ENSP00000442050.2	Q99447-3
	PCYT2	ENST00000883690.1		c.*79C>T		3_prime_UTR	Exon 15 of 15	ENSP00000553749.1

Frequencies

GnomAD3 genomes AF: 0.0397 AC: 6048 AN: 152200 Hom.: 160 Cov.: 33

Gnomad AFR AF: 0.0104

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0279

Gnomad ASJ AF: 0.0726

Gnomad EAS AF: 0.0204

Gnomad SAS AF: 0.0977

Gnomad FIN AF: 0.0468

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0554

Gnomad OTH AF: 0.0363

GnomAD4 exome AF: 0.0532 AC: 40100 AN: 754290 Hom.: 1258 Cov.: 10 AF XY: 0.0544 AC XY: 20887 AN XY: 384256

African (AFR) AF: 0.00904 AC: 172 AN: 19036

American (AMR) AF: 0.0208 AC: 523 AN: 25116

Ashkenazi Jewish (ASJ) AF: 0.0709 AC: 1203 AN: 16970

East Asian (EAS) AF: 0.0182 AC: 605 AN: 33186

South Asian (SAS) AF: 0.0894 AC: 5115 AN: 57208

European-Finnish (FIN) AF: 0.0522 AC: 1715 AN: 32824

Middle Eastern (MID) AF: 0.0376 AC: 159 AN: 4230

European-Non Finnish (NFE) AF: 0.0543 AC: 28761 AN: 529424

Other (OTH) AF: 0.0509 AC: 1847 AN: 36296

GnomAD4 genome AF: 0.0397 AC: 6051 AN: 152318 Hom.: 160 Cov.: 33 AF XY: 0.0400 AC XY: 2977 AN XY: 74488

African (AFR) AF: 0.0103 AC: 430 AN: 41568

American (AMR) AF: 0.0278 AC: 426 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0726 AC: 252 AN: 3472

East Asian (EAS) AF: 0.0204 AC: 106 AN: 5194

South Asian (SAS) AF: 0.0978 AC: 472 AN: 4828

European-Finnish (FIN) AF: 0.0468 AC: 497 AN: 10614

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0554 AC: 3765 AN: 68018

Other (OTH) AF: 0.0388 AC: 82 AN: 2114

Alfa AF: 0.0517 Hom.: 42

Bravo AF: 0.0344

Asia WGS AF: 0.0740 AC: 256 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.44
PhyloP100		-0.96
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	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: rs7405872; hg19: chr17-79862630;