12-57829560-C-A

Variant names:

• chr12-57829560-C-A
• NM_005730.4:c.101G>T

Variant summary

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

The NM_005730.4(CTDSP2):​c.101G>T​(p.Gly34Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CTDSP2 NM_005730.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.20

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]

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=0.24224386).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTDSP2	NM_005730.4	c.101G>T	p.Gly34Val	missense_variant	Exon 2 of 8	ENST00000398073.7	NP_005721.3
CTDSP2	XM_005268556.3	c.101G>T	p.Gly34Val	missense_variant	Exon 2 of 8		XP_005268613.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTDSP2	ENST00000398073.7	c.101G>T	p.Gly34Val	missense_variant	Exon 2 of 8	1	NM_005730.4	ENSP00000381148.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 22, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.101G>T (p.G34V) alteration is located in exon 2 (coding exon 2) of the CTDSP2 gene. This alteration results from a G to T substitution at nucleotide position 101, causing the glycine (G) at amino acid position 34 to be replaced by a valine (V). 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	0.14
BayesDel_addAF	Uncertain	0.017	T
BayesDel_noAF	Benign	-0.21
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T;T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.24	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M;.
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-2.9	D;D
REVEL	Benign	0.19
Sift	Benign	0.21	T;D
Sift4G	Benign	0.40	T;D
Polyphen		0.010	B;D
Vest4		0.42
MutPred		0.36		Loss of disorder (P = 0.0597);Loss of disorder (P = 0.0597);
MVP		0.47
MPC		0.79
ClinPred		0.95	D
GERP RS		4.7
Varity_R		0.45
gMVP		0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr12-58223343;