17-39531119-A-G

Position:

• chr17-39531119-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016507.4(CDK12):​c.4276A>G​(p.Ser1426Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDK12 NM_016507.4 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 4.78

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11809811).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDK12	NM_016507.4	c.4276A>G	p.Ser1426Gly	missense_variant	14/14	ENST00000447079.6	NP_057591.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDK12	ENST00000447079.6	c.4276A>G	p.Ser1426Gly	missense_variant	14/14	1	NM_016507.4	ENSP00000398880.4
CDK12	ENST00000430627.6	c.4249A>G	p.Ser1417Gly	missense_variant	14/14	1		ENSP00000407720.2
CDK12	ENST00000584336.1	n.1238A>G		non_coding_transcript_exon_variant	1/1	6
CDK12	ENST00000559663.2	n.3760+4803A>G		intron_variant		5		ENSP00000453329.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not specified Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.031	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.053	.;T
Eigen	Benign	-0.10
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.75	T;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	1.4	.;L
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.060	N;N
REVEL	Benign	0.11
Sift	Uncertain	0.0040	D;D
Sift4G	Benign	0.51	T;T
Polyphen		0.0	B;B
Vest4		0.11
MutPred		0.23		.;Loss of disorder (P = 0.1245);
MVP		0.45
MPC		0.21
ClinPred		0.42	T
GERP RS		5.5
Varity_R		0.20
gMVP		0.16

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: rs587778178; hg19: chr17-37687372;