Variant chr17-39462785-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_016507.4(CDK12):c.714G>A(p.Ser238=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00971 in 1,614,046 control chromosomes in the GnomAD database, including 1,283 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.052 ( 665 hom., cov: 32)

Exomes 𝑓: 0.0053 ( 618 hom. )

Consequence

CDK12
NM_016507.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -4.03

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 17-39462785-G-A is Benign according to our data. Variant chr17-39462785-G-A is described in ClinVar as [Benign]. Clinvar id is 1250047.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.03 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDK12	NM_016507.4 linkuse as main transcript	c.714G>A	p.Ser238=	synonymous_variant	1/14	ENST00000447079.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDK12	ENST00000447079.6 linkuse as main transcript	c.714G>A	p.Ser238=	synonymous_variant	1/14	1	NM_016507.4	P4	Q9NYV4-1
CDK12	ENST00000430627.6 linkuse as main transcript	c.714G>A	p.Ser238=	synonymous_variant	1/14	1		A1	Q9NYV4-2
CDK12	ENST00000584632.5 linkuse as main transcript	c.714G>A	p.Ser238=	synonymous_variant	1/13	5
CDK12	ENST00000559663.2 linkuse as main transcript	c.714G>A	p.Ser238=	synonymous_variant, NMD_transcript_variant	1/21	5

Frequencies

GnomAD3 genomes

AF:

0.0518

AC:

7878

AN:

152058

Hom.:

665

Cov.:

show subpopulations

Gnomad AFR

AF:

0.180

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0190

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000579

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000779

Gnomad OTH

AF:

0.0339

GnomAD3 exomes

AF:

0.0141

AC:

3531

AN:

251180

Hom.:

268

AF XY:

0.0101

AC XY:

1367

AN XY:

135838

show subpopulations

Gnomad AFR exome

AF:

0.187

Gnomad AMR exome

AF:

0.0112

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000719

Gnomad FIN exome

AF:

0.000370

Gnomad NFE exome

AF:

0.000352

Gnomad OTH exome

AF:

0.00603

GnomAD4 exome

AF:

0.00531

AC:

7767

AN:

1461870

Hom.:

618

Cov.:

AF XY:

0.00445

AC XY:

3238

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.183

Gnomad4 AMR exome

AF:

0.0117

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000742

Gnomad4 FIN exome

AF:

0.000543

Gnomad4 NFE exome

AF:

0.000228

Gnomad4 OTH exome

AF:

0.0122

GnomAD4 genome

AF:

0.0519

AC:

7898

AN:

152176

Hom.:

665

Cov.:

AF XY:

0.0505

AC XY:

3761

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.180

Gnomad4 AMR

AF:

0.0189

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000580

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.000779

Gnomad4 OTH

AF:

0.0354

Alfa

AF:

0.0207

Hom.:

158

Bravo

AF:

0.0600

Asia WGS

AF:

0.0200

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

CDK12-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 28, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 15, 2019

- -

Hereditary breast ovarian cancer syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

National Health Laboratory Service, Universitas Academic Hospital and University of the Free State

Apr 19, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.58

DANN

Benign

0.75

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over