rs2453274

chr15-44482004-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016396.3(CTDSPL2):c.187-2220C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0555 in 152,284 control chromosomes in the GnomAD database, including 401 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.055 (401 hom., cov: 32)
• Consequence: CTDSPL2 NM_016396.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.633

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0776 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTDSPL2	NM_016396.3	c.187-2220C>T		intron_variant		ENST00000260327.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTDSPL2	ENST00000260327.9	c.187-2220C>T		intron_variant		1	NM_016396.3	P1

Frequencies

GnomAD3 genomes AF: 0.0555 AC: 8451 AN: 152166 Hom.: 401 Cov.: 32

Gnomad AFR AF: 0.0135

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0345

Gnomad ASJ AF: 0.0141

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0174

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0793

Gnomad OTH AF: 0.0454

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0555 AC: 8451 AN: 152284 Hom.: 401 Cov.: 32 AF XY: 0.0571 AC XY: 4254 AN XY: 74462

Gnomad4 AFR AF: 0.0134

Gnomad4 AMR AF: 0.0343

Gnomad4 ASJ AF: 0.0141

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0178

Gnomad4 FIN AF: 0.159

Gnomad4 NFE AF: 0.0793

Gnomad4 OTH AF: 0.0449

Alfa AF: 0.0709 Hom.: 594

Bravo AF: 0.0465

Asia WGS AF: 0.0110 AC: 37 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.3
Dann	Benign	0.64

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: rs2453274; hg19: chr15-44774202;