Genetic Variant CTDSP2:c.-242C>T (chr12-57827589-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000547701.5(CTDSP2):c.-242C>T variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.00000372 in 1,613,922 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

CTDSP2
ENST00000547701.5 5_prime_UTR_premature_start_codon_gain

Scores

Splicing: ADA: 0.7329

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.90

Variant links:

Genes affected

CTDSP2 (HGNC:17077): (CTD small phosphatase 2) Enables RNA polymerase II CTD heptapeptide repeat phosphatase activity. Involved in protein dephosphorylation. Predicted to be located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

CTDSP2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19614372).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTDSP2	NM_005730.4 link	c.215C>T	p.Ser72Leu	missense_variant, splice_region_variant	Exon 3 of 8	ENST00000398073.7	NP_005721.3	O14595A0A024RBA6
CTDSP2	XM_005268556.3 link	c.215C>T	p.Ser72Leu	missense_variant, splice_region_variant	Exon 3 of 8		XP_005268613.1	A0A024RB65

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTDSP2	ENST00000398073.7 link	c.215C>T	p.Ser72Leu	missense_variant, splice_region_variant	Exon 3 of 8	1	NM_005730.4	ENSP00000381148.2		O14595

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461660

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727116

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152262

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

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

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.215C>T (p.S72L) alteration is located in exon 3 (coding exon 3) of the CTDSP2 gene. This alteration results from a C to T substitution at nucleotide position 215, causing the serine (S) at amino acid position 72 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.031

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.084

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.82

M_CAP

Benign

0.0096

MetaRNN

Benign

0.20

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-1.8

REVEL

Benign

0.23

Sift

Benign

0.25

Sift4G

Benign

0.36

Polyphen

0.0030

Vest4

0.40

MutPred

0.44

Loss of sheet (P = 0.0126);

MVP

0.30

MPC

0.55

ClinPred

0.73

GERP RS

4.3

Varity_R

0.16

gMVP

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.73

dbscSNV1_RF

Benign

0.59

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