12-57823637-C-A

Variant names:

• chr12-57823637-C-A
• rs1050127790
• NM_005730.4:c.781G>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_005730.4(CTDSP2):​c.781G>T​(p.Val261Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V261I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CTDSP2 NM_005730.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.99
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.808

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005730.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTDSP2	NM_005730.4	MANE Select	c.781G>T	p.Val261Phe	missense	Exon 8 of 8	NP_005721.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTDSP2	ENST00000398073.7	TSL:1 MANE Select	c.781G>T	p.Val261Phe	missense	Exon 8 of 8	ENSP00000381148.2	O14595
	CTDSP2	ENST00000547701.5	TSL:1	c.325G>T	p.Val109Phe	missense	Exon 8 of 8	ENSP00000446705.1	F8W184
	CTDSP2	ENST00000548823.1	TSL:1	c.262G>T	p.Val88Phe	missense	Exon 4 of 4	ENSP00000447046.1	F8W1I1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.049	D
MetaRNN	Pathogenic	0.81	D
MetaSVM	Benign	-0.63	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		5.0
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-4.4	D
REVEL	Uncertain	0.39
Sift	Benign	0.035	D
Sift4G	Uncertain	0.026	D
Polyphen		1.0	D
Vest4		0.91
MutPred		0.68		Loss of helix (P = 0.1706)
MVP		0.59
MPC		1.8
ClinPred		0.99	D
GERP RS		5.3
Varity_R		0.87
gMVP		0.97
Mutation Taster		=35/65	disease causing

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

Other links and lift over

dbSNP: rs1050127790; hg19: chr12-58217420;