rs1060499745

chr16-89694721-C-Gchr16-89694721-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PP3 PP5_Moderate

The NM_052988.5(CDK10):c.725C>G(p.Thr242Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDK10 NM_052988.5 missense
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 2.52

Genes affected

CDK10 (HGNC:1770): (cyclin dependent kinase 10) The protein encoded by this gene belongs to the CDK subfamily of the Ser/Thr protein kinase family. The CDK subfamily members are highly similar to the gene products of S. cerevisiae cdc28, and S. pombe cdc2, and are known to be essential for cell cycle progression. This kinase has been shown to play a role in cellular proliferation and its function is limited to cell cycle G2-M phase. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
• PP5: Variant 16-89694721-C-G is Pathogenic according to our data. Variant chr16-89694721-C-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 402153.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-89694721-C-G is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDK10	NM_052988.5	c.725C>G	p.Thr242Ser	missense_variant	10/13	ENST00000353379.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDK10	ENST00000353379.12	c.725C>G	p.Thr242Ser	missense_variant	10/13	1	NM_052988.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Abnormal brain morphology Pathogenic:1

Likely pathogenic, criteria provided, single submitter

research

Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
Cadd	Uncertain	24
Dann	Benign	0.78
DEOGEN2	Benign	0.0036	T;T;.;.;.
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.22
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.71	T;T;.;T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.13	T;T;T;T;T
MetaSVM	Benign	-0.92	T
MutationTaster	Benign	0.63	D;D;D
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.20	N;N;N;N;.
REVEL	Benign	0.052
Sift	Benign	0.19	T;T;T;T;.
Sift4G	Benign	0.23	T;T;T;T;T
Polyphen		0.0, 0.0010	.;B;B;.;B
Vest4		0.33
MutPred		0.27		.;Gain of disorder (P = 0.0291);.;.;.;
MVP		0.38
MPC		0.090
ClinPred		0.42	T
GERP RS		4.3
Varity_R		0.094
gMVP		0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.72		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.72		Position offset: 1

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

Publications

LitVar

Other links and lift over

dbSNP: rs1060499745; hg19: chr16-89761129;