12-57823671-G-C

Variant names:

• chr12-57823671-G-C
• rs752232234
• NM_005730.4:c.747C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005730.4(CTDSP2):​c.747C>G​(p.Ile249Met) 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. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. I249I) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CTDSP2 NM_005730.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0160
• Publications: 0 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3989084).

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.747C>G	p.Ile249Met	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.747C>G	p.Ile249Met	missense	Exon 8 of 8	ENSP00000381148.2	O14595
	CTDSP2	ENST00000547701.5	TSL:1	c.291C>G	p.Ile97Met	missense	Exon 8 of 8	ENSP00000446705.1	F8W184
	CTDSP2	ENST00000548823.1	TSL:1	c.228C>G	p.Ile76Met	missense	Exon 4 of 4	ENSP00000447046.1	F8W1I1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.034	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Benign	0.17
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PhyloP100		-0.016
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.25
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.037	D
Polyphen		0.78	P
Vest4		0.38
MutPred		0.57		Loss of stability (P = 0.1031)
MVP		0.52
MPC		1.5
ClinPred		0.79	D
GERP RS		2.3
Varity_R		0.76
gMVP		0.65
Mutation Taster		=60/40	polymorphism

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: rs752232234; hg19: chr12-58217454;