rs7503195

Variant names:

• chr17-39566262-G-A
• rs7503195
• ENST00000559663.2:n.*872-526G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-39566262-G-A
• chr17-39566262-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000559663.2(CDK12):​n.*872-526G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 152,032 control chromosomes in the GnomAD database, including 9,718 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 0.33 (9718 hom., cov: 32)
• Consequence: CDK12 ENST00000559663.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15
• Publications: 10 publications found

Genes affected

CDK12 (HGNC:24224): (cyclin dependent kinase 12) Enables RNA polymerase II CTD heptapeptide repeat kinase activity and cyclin binding activity. Involved in phosphorylation of RNA polymerase II C-terminal domain; protein autophosphorylation; and regulation of MAP kinase activity. Located in nuclear speck. Part of cyclin K-CDK12 complex. [provided by Alliance of Genome Resources, Apr 2022]

CDK12 Gene-Disease associations (from GenCC):

• Tourette syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000559663.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK12	ENST00000559663.2	TSL:5	n.*872-526G>A		intron	N/A	ENSP00000453329.2

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50536 AN: 151914 Hom.: 9715 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.500

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.365

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

GnomAD4 genome AF: 0.332 AC: 50535 AN: 152032 Hom.: 9718 Cov.: 32 AF XY: 0.336 AC XY: 24960 AN XY: 74294

African (AFR) AF: 0.131 AC: 5449 AN: 41514

American (AMR) AF: 0.366 AC: 5586 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.394 AC: 1369 AN: 3472

East Asian (EAS) AF: 0.471 AC: 2430 AN: 5156

South Asian (SAS) AF: 0.500 AC: 2400 AN: 4798

European-Finnish (FIN) AF: 0.392 AC: 4143 AN: 10556

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.411 AC: 27954 AN: 67956

Other (OTH) AF: 0.360 AC: 758 AN: 2106

Alfa AF: 0.384 Hom.: 9147

Bravo AF: 0.318

Asia WGS AF: 0.457 AC: 1587 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.6
DANN	Benign	0.65
PhyloP100		1.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7503195; hg19: chr17-37722515;