17-81904754-G-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002861.5(PCYT2):​c.*79C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000133 in 754,570 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000013 (0 hom.)
• Consequence: PCYT2 NM_002861.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.957
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

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>A		3_prime_UTR	Exon 13 of 13	NP_002852.1	Q99447-1
	PCYT2	NM_001184917.3		c.*79C>A		3_prime_UTR	Exon 14 of 14	NP_001171846.1	Q99447-3
	PCYT2	NM_001330518.2		c.*79C>A		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>A		3_prime_UTR	Exon 13 of 13	ENSP00000439245.3	Q99447-1
	PCYT2	ENST00000538721.6	TSL:1	c.*79C>A		3_prime_UTR	Exon 14 of 14	ENSP00000442050.2	Q99447-3
	PCYT2	ENST00000883690.1		c.*79C>A		3_prime_UTR	Exon 15 of 15	ENSP00000553749.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000133 AC: 1 AN: 754570 Hom.: 0 Cov.: 10 AF XY: 0.00000260 AC XY: 1 AN XY: 384402

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 19036

American (AMR) AF: 0.00 AC: 0 AN: 25116

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16972

East Asian (EAS) AF: 0.0000301 AC: 1 AN: 33188

South Asian (SAS) AF: 0.00 AC: 0 AN: 57234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32826

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4232

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 529662

Other (OTH) AF: 0.00 AC: 0 AN: 36304

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.40
DANN	Benign	0.56
PhyloP100		-0.96
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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;