15-44490999-G-A

Position:

• chr15-44490999-G-A

Variant summary

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

The NM_016396.3(CTDSPL2):​c.691G>A​(p.Ala231Thr) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CTDSPL2 NM_016396.3 missense, splice_region
• Scores: Splicing: ADA: 1.000
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.12

Genes affected

CTDSPL2 (HGNC:26936): (CTD small phosphatase like 2) Enables RNA polymerase II CTD heptapeptide repeat phosphatase activity. Predicted to act upstream of or within negative regulation of BMP signaling pathway; positive regulation of protein export from nucleus; and protein dephosphorylation. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

CTDSPL2 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTDSPL2	NM_016396.3	c.691G>A	p.Ala231Thr	missense_variant, splice_region_variant	5/13	ENST00000260327.9	NP_057480.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTDSPL2	ENST00000260327.9	c.691G>A	p.Ala231Thr	missense_variant, splice_region_variant	5/13	1	NM_016396.3	ENSP00000260327.4
CTDSPL2	ENST00000558966.5	c.691G>A	p.Ala231Thr	missense_variant, splice_region_variant	5/13	1		ENSP00000452837.1
CTDSPL2	ENST00000558373.5	c.475+4299G>A		intron_variant		1		ENSP00000453051.1
CTDSPL2	ENST00000561189.1	n.8G>A		splice_region_variant, non_coding_transcript_exon_variant	1/5	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center

Jul 06, 2021

BP4, PS2, PM2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.098	T
BayesDel_noAF	Benign	-0.38
CADD	Pathogenic	43
DANN	Uncertain	1.0
DEOGEN2	Benign	0.022	T;T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.84	.;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.34	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M;M
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.58	N;N
REVEL	Benign	0.14
Sift	Uncertain	0.0080	D;D
Sift4G	Benign	0.40	T;T
Polyphen		0.79	P;P
Vest4		0.54
MutPred		0.33		Gain of glycosylation at A231 (P = 7e-04);Gain of glycosylation at A231 (P = 7e-04);
MVP		0.12
MPC		0.16
ClinPred		0.82	D
GERP RS		4.8
RBP_binding_hub_radar		0.67
RBP_regulation_power_radar		2.4
Varity_R		0.15
gMVP		0.36

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	1.0
SpliceAI score (max)		0.83		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.83		Position offset: 0

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: chr15-44783197;