NM_005730.4:c.412-280C>T

Variant names:

• chr12-57824599-G-A
• rs41292017
• NM_005730.4:c.412-280C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_005730.4(CTDSP2):​c.412-280C>T variant causes a intron change. The variant allele was found at a frequency of 0.0146 in 620,694 control chromosomes in the GnomAD database, including 99 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 0.012 (9 hom., cov: 32)
  • Exomes 𝑓: 0.016 (90 hom.)
• Consequence: CTDSP2 NM_005730.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.00
• Publications: 9 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]

MIR26A2 (HGNC:31611): (microRNA 26a-2) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0115 (1756/152332) while in subpopulation SAS AF = 0.0236 (114/4824). AF 95% confidence interval is 0.0201. There are 9 homozygotes in GnomAd4. There are 819 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

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.412-280C>T		intron	N/A	NP_005721.3
	MIR26A2	NR_029847.1		n.*10C>T		downstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTDSP2	ENST00000398073.7	TSL:1 MANE Select	c.412-280C>T		intron	N/A	ENSP00000381148.2	O14595
	CTDSP2	ENST00000547701.5	TSL:1	c.-45-280C>T		intron	N/A	ENSP00000446705.1	F8W184
	CTDSP2	ENST00000548823.1	TSL:1	c.118-642C>T		intron	N/A	ENSP00000447046.1	F8W1I1

Frequencies

GnomAD3 genomes AF: 0.0115 AC: 1752 AN: 152214 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.00251

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0135

Gnomad ASJ AF: 0.0228

Gnomad EAS AF: 0.0202

Gnomad SAS AF: 0.0234

Gnomad FIN AF: 0.00480

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0153

Gnomad OTH AF: 0.0153

GnomAD2 exomes AF: 0.0153 AC: 3797 AN: 247932 AF XY: 0.0161

Gnomad AFR exome AF: 0.00233

Gnomad AMR exome AF: 0.00909

Gnomad ASJ exome AF: 0.0280

Gnomad EAS exome AF: 0.0219

Gnomad FIN exome AF: 0.00749

Gnomad NFE exome AF: 0.0163

Gnomad OTH exome AF: 0.0186

GnomAD4 exome AF: 0.0156 AC: 7326 AN: 468362 Hom.: 90 Cov.: 0 AF XY: 0.0162 AC XY: 4227 AN XY: 260570

African (AFR) AF: 0.00241 AC: 33 AN: 13686

American (AMR) AF: 0.00932 AC: 359 AN: 38540

Ashkenazi Jewish (ASJ) AF: 0.0291 AC: 455 AN: 15624

East Asian (EAS) AF: 0.0195 AC: 416 AN: 21306

South Asian (SAS) AF: 0.0207 AC: 1388 AN: 67012

European-Finnish (FIN) AF: 0.00755 AC: 285 AN: 37738

Middle Eastern (MID) AF: 0.0226 AC: 53 AN: 2346

European-Non Finnish (NFE) AF: 0.0158 AC: 3937 AN: 249352

Other (OTH) AF: 0.0176 AC: 400 AN: 22758

GnomAD4 genome AF: 0.0115 AC: 1756 AN: 152332 Hom.: 9 Cov.: 32 AF XY: 0.0110 AC XY: 819 AN XY: 74486

African (AFR) AF: 0.00250 AC: 104 AN: 41574

American (AMR) AF: 0.0135 AC: 206 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0228 AC: 79 AN: 3470

East Asian (EAS) AF: 0.0202 AC: 105 AN: 5186

South Asian (SAS) AF: 0.0236 AC: 114 AN: 4824

European-Finnish (FIN) AF: 0.00480 AC: 51 AN: 10622

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0153 AC: 1042 AN: 68028

Other (OTH) AF: 0.0161 AC: 34 AN: 2116

Alfa AF: 0.0156 Hom.: 5

Bravo AF: 0.0123

Asia WGS AF: 0.0270 AC: 94 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	12
DANN	Benign	0.73
PhyloP100		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs41292017; hg19: chr12-58218382;