2-218401648-G-C

Variant names:

• chr2-218401648-G-C
• rs1455941412
• NM_021198.3:c.152G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021198.3(CTDSP1):​c.152G>C​(p.Gly51Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,286 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign 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. G51E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: CTDSP1 NM_021198.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.95

Genes affected

CTDSP1 (HGNC:21614): (CTD small phosphatase 1) This gene encodes a member of the small C-terminal domain phosphatase (SCP) family of nuclear phosphatases. These proteins play a role in transcriptional regulation through specific dephosphorylation of phosphoserine 5 within tandem heptapeptide repeats of the C-terminal domain of RNA polymerase II. The encoded protein plays a role in neuronal gene silencing in non-neuronal cells, and may also inhibit osteoblast differentiation. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06334895).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTDSP1	NM_021198.3	c.152G>C	p.Gly51Ala	missense_variant	Exon 2 of 7	ENST00000273062.7	NP_067021.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTDSP1	ENST00000273062.7	c.152G>C	p.Gly51Ala	missense_variant	Exon 2 of 7	1	NM_021198.3	ENSP00000273062.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000401 AC: 1 AN: 249082 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 134778

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000547

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1460286 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726462

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

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.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	15
DANN	Benign	0.77
DEOGEN2	Benign	0.012	.;T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.76	T;T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.063	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.55	N;N
PrimateAI	Benign	0.42	T
PROVEAN	Benign	0.18	N;N
REVEL	Benign	0.068
Sift	Benign	0.74	T;T
Sift4G	Benign	0.62	T;T
Polyphen		0.0	.;B
Vest4		0.20
MutPred		0.40		Loss of loop (P = 0.0389);Loss of loop (P = 0.0389);
MVP		0.22
MPC		0.050
ClinPred		0.044	T
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.065
gMVP		0.34

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

Other links and lift over

dbSNP: rs1455941412; hg19: chr2-219266371;