Variant X-16609606-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_175859.3(CTPS2):c.1626G>C(p.Gly542Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000304 in 1,209,204 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 101 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., 47 hem., cov: 23)

Exomes 𝑓: 0.00018 ( 0 hom. 54 hem. )

Consequence

CTPS2
NM_175859.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.64

Variant links:

Genes affected

CTPS2 (HGNC:2520): (CTP synthase 2) The protein encoded by this gene catalyzes the formation of CTP from UTP with the concomitant deamination of glutamine to glutamate. This protein is the rate-limiting enzyme in the synthesis of cytosine nucleotides, which play an important role in various metabolic processes and provide the precursors necessary for the synthesis of RNA and DNA. Cancer cells that exhibit increased cell proliferation also exhibit an increased activity of this encoded protein. Thus, this protein is an attractive target for selective chemotherapy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

CTPS2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant X-16609606-C-G is Benign according to our data. Variant chrX-16609606-C-G is described in ClinVar as [Benign]. Clinvar id is 721651.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.64 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 47 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTPS2	NM_175859.3 linkuse as main transcript	c.1626G>C	p.Gly542Gly	synonymous_variant	17/19	ENST00000359276.9	NP_787055.1	Q9NRF8A0A024RC00

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CTPS2	ENST00000359276.9 linkuse as main transcript	c.1626G>C	p.Gly542Gly	synonymous_variant	17/19	1	NM_175859.3	ENSP00000352222.4	Q9NRF8
CTPS2	ENST00000380241.7 linkuse as main transcript	c.1626G>C	p.Gly542Gly	synonymous_variant	17/19	1		ENSP00000369590.3	Q9NRF8
CTPS2	ENST00000443824.5 linkuse as main transcript	c.1626G>C	p.Gly542Gly	synonymous_variant	17/19	2		ENSP00000401264.1	Q9NRF8

Frequencies

GnomAD3 genomes

AF:

0.00147

AC:

164

AN:

111550

Hom.:

Cov.:

AF XY:

0.00139

AC XY:

AN XY:

33740

show subpopulations

Gnomad AFR

AF:

0.00532

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000957

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000409

AC:

AN:

183356

Hom.:

AF XY:

0.000265

AC XY:

AN XY:

67800

show subpopulations

Gnomad AFR exome

AF:

0.00479

Gnomad AMR exome

AF:

0.000109

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000525

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000733

Gnomad OTH exome

AF:

0.000442

GnomAD4 exome

AF:

0.000185

AC:

203

AN:

1097602

Hom.:

Cov.:

AF XY:

0.000149

AC XY:

AN XY:

362964

show subpopulations

Gnomad4 AFR exome

AF:

0.00584

Gnomad4 AMR exome

AF:

0.000142

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000331

Gnomad4 SAS exome

AF:

0.0000924

Gnomad4 FIN exome

AF:

0.0000493

Gnomad4 NFE exome

AF:

0.0000202

Gnomad4 OTH exome

AF:

0.000391

GnomAD4 genome

AF:

0.00147

AC:

164

AN:

111602

Hom.:

Cov.:

AF XY:

0.00139

AC XY:

AN XY:

33802

show subpopulations

Gnomad4 AFR

AF:

0.00530

Gnomad4 AMR

AF:

0.0000956

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000477

Hom.:

Bravo

AF:

0.00145

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 05, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.12

DANN

Benign

0.46

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over