Genetic Variant NM_005730.4:c.412-280C>T (chr12-57824599-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.00

Publications

9 publications found

Variant links:

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]

CTDSP2 links:

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]

MIR26A2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTDSP2	NM_005730.4 link	c.412-280C>T		intron_variant	Intron 5 of 7	ENST00000398073.7	NP_005721.3	O14595A0A024RBA6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTDSP2	ENST00000398073.7 link	c.412-280C>T		intron_variant	Intron 5 of 7	1	NM_005730.4	ENSP00000381148.2		O14595

Frequencies

GnomAD3 genomes

AF:

0.0115

AC:

1752

AN:

152214

Hom.:

Cov.:

show subpopulations

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

show subpopulations

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.:

Cov.:

AF XY:

0.0162

AC XY:

4227

AN XY:

260570

show subpopulations

African (AFR)

AF:

0.00241

AC:

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:

AN:

2346

European-Non Finnish (NFE)

AF:

0.0158

AC:

3937

AN:

249352

Other (OTH)

AF:

0.0176

AC:

400

AN:

22758

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

420

839

1259

1678

2098

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

114

152

190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0115

AC:

1756

AN:

152332

Hom.:

Cov.:

AF XY:

0.0110

AC XY:

819

AN XY:

74486

show subpopulations

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:

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:

AN:

10622

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0153

AC:

1042

AN:

68028

Other (OTH)

AF:

0.0161

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

178

267

356

445

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0156

Hom.:

Bravo

AF:

0.0123

Asia WGS

AF:

0.0270

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

(source)

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)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over