chr2-218401677-C-G

Variant names:

• chr2-218401677-C-G
• rs748388380
• NM_021198.3:c.181C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021198.3(CTDSP1):​c.181C>G​(p.Pro61Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000225 in 1,602,366 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: CTDSP1 NM_021198.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.92
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26353285).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021198.3. 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
	CTDSP1	NM_021198.3	MANE Select	c.181C>G	p.Pro61Ala	missense	Exon 2 of 7	NP_067021.1	Q9GZU7-1
	CTDSP1	NM_001400269.1		c.181C>G	p.Pro61Ala	missense	Exon 2 of 6	NP_001387198.1
	CTDSP1	NM_001400270.1		c.181C>G	p.Pro61Ala	missense	Exon 2 of 6	NP_001387199.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTDSP1	ENST00000273062.7	TSL:1 MANE Select	c.181C>G	p.Pro61Ala	missense	Exon 2 of 7	ENSP00000273062.2	Q9GZU7-1
	CTDSP1	ENST00000885505.1		c.181C>G	p.Pro61Ala	missense	Exon 2 of 7	ENSP00000555564.1
	CTDSP1	ENST00000452977.6	TSL:5	c.181C>G	p.Pro61Ala	missense	Exon 2 of 7	ENSP00000404301.2	H7C270

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152118 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000839 AC: 2 AN: 238390 AF XY: 0.00000774

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000186

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000228 AC: 33 AN: 1450248 Hom.: 0 Cov.: 32 AF XY: 0.0000250 AC XY: 18 AN XY: 721010

African (AFR) AF: 0.00 AC: 0 AN: 32998

American (AMR) AF: 0.00 AC: 0 AN: 42784

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25330

East Asian (EAS) AF: 0.00 AC: 0 AN: 39544

South Asian (SAS) AF: 0.00 AC: 0 AN: 85002

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52762

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5726

European-Non Finnish (NFE) AF: 0.0000298 AC: 33 AN: 1106324

Other (OTH) AF: 0.00 AC: 0 AN: 59778

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152118 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74296

African (AFR) AF: 0.0000483 AC: 2 AN: 41430

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.056	T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.022
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.0096	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		3.9
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.13
Sift	Benign	0.15	T
Sift4G	Uncertain	0.047	D
Polyphen		0.053	B
Vest4		0.44
MutPred		0.39		Loss of stability (P = 0.0656)
MVP		0.31
MPC		0.32
ClinPred		0.87	D
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.45
Mutation Taster		=63/37	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: rs748388380; hg19: chr2-219266400;