chr15-44484268-T-G

Position:

• chr15-44484268-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016396.3(CTDSPL2):​c.231T>G​(p.Asp77Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 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)
• Consequence: CTDSPL2 NM_016396.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.93

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]

ACMG classification

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=0.23509574).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTDSPL2	NM_016396.3	c.231T>G	p.Asp77Glu	missense_variant	3/13	ENST00000260327.9	NP_057480.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTDSPL2	ENST00000260327.9	c.231T>G	p.Asp77Glu	missense_variant	3/13	1	NM_016396.3	ENSP00000260327.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 20, 2024

The c.231T>G (p.D77E) alteration is located in exon 3 (coding exon 2) of the CTDSPL2 gene. This alteration results from a T to G substitution at nucleotide position 231, causing the aspartic acid (D) at amino acid position 77 to be replaced by a glutamic acid (E). 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	0.12
BayesDel_addAF	Uncertain	0.047	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.016	T;T;T;T;.;.
Eigen	Benign	-0.12
Eigen_PC	Benign	0.064
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.86	.;D;D;D;D;D
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.24	T;T;T;T;T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.8	L;.;L;.;.;L
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.51	N;N;N;D;D;N
REVEL	Benign	0.24
Sift	Benign	0.26	T;T;T;T;T;D
Sift4G	Benign	0.69	T;T;T;T;T;T
Polyphen		0.068	B;.;B;.;.;P
Vest4		0.39
MutPred		0.24		Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);
MVP		0.43
MPC		0.11
ClinPred		0.86	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.059
gMVP		0.14

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-44776466;