Variant chr15-44459068-A-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_016396.3(CTDSPL2):c.54A>C(p.Gln18His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,459,432 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CTDSPL2
NM_016396.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.100

Variant links:

Genes affected

CTDSPL2 (HGNC:26936): (CTD small phosphatase like 2) Enables RNA polymerase II CTD heptapeptide repeat phosphatase activity. Predicted to act upstream of or within negative regulation of BMP signaling pathway; positive regulation of protein export from nucleus; and protein dephosphorylation. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

CTDSPL2 links:

CTDSPL2 (HGNC:):

CTDSPL2 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=0.087717235).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTDSPL2	NM_016396.3 linkuse as main transcript	c.54A>C	p.Gln18His	missense_variant	2/13	ENST00000260327.9	NP_057480.2	Q05D32-1A0A024R5Q8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTDSPL2	ENST00000260327.9 linkuse as main transcript	c.54A>C	p.Gln18His	missense_variant	2/13	1	NM_016396.3	ENSP00000260327.4		Q05D32-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1459432

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726126

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 06, 2023

The c.54A>C (p.Q18H) alteration is located in exon 2 (coding exon 1) of the CTDSPL2 gene. This alteration results from a A to C substitution at nucleotide position 54, causing the glutamine (Q) at amino acid position 18 to be replaced by a histidine (H). 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

0.097

BayesDel_addAF

Benign

-0.048

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.014

T;T;T;T;.;.

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.85

.;T;T;D;T;T

M_CAP

Benign

0.032

MetaRNN

Benign

0.088

T;T;T;T;T;T

MetaSVM

Benign

-0.51

MutationAssessor

Benign

1.4

L;.;L;.;.;L

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.87

N;N;N;D;D;N

REVEL

Benign

0.22

Sift

Benign

0.046

D;T;D;T;T;D

Sift4G

Benign

0.12

T;T;T;T;T;T

Polyphen

0.011

B;.;B;.;.;P

Vest4

0.32

MutPred

0.18

Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);

MVP

0.38

MPC

0.15

ClinPred

0.34

GERP RS

-3.7

Varity_R

0.078

gMVP

0.17

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