rs17537669

Variant names:

• chr7-39951707-C-G
• rs17537669
• NM_003718.5:c.1066C>G

Your query was ambiguous. Multiple possible variants found:

• chr7-39951707-C-G
• chr7-39951707-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_003718.5(CDK13):​c.1066C>G​(p.Pro356Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00337 in 1,471,084 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0025 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0035 (14 hom.)
• Consequence: CDK13 NM_003718.5 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.207
• Publications: 5 publications found

Genes affected

CDK13 (HGNC:1733): (cyclin dependent kinase 13) The protein encoded by this gene is a member of the cyclin-dependent serine/threonine protein kinase family. Members of this family are well known for their essential roles as master switches in cell cycle control. The exact function of this protein has not yet been determined, but it may play a role in mRNA processing and may be involved in regulation of hematopoiesis. Alternatively spliced transcript variants have been described.[provided by RefSeq, Dec 2009]

CDK13 Gene-Disease associations (from GenCC):

• congenital heart defects, dysmorphic facial features, and intellectual developmental disorder

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Illumina
• syndromic intellectual disability

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.006324768).
• BP6: Variant 7-39951707-C-G is Benign according to our data. Variant chr7-39951707-C-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 446011.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00252 (384/152132) while in subpopulation NFE AF = 0.00443 (301/67974). AF 95% confidence interval is 0.00402. There are 1 homozygotes in GnomAd4. There are 175 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 384 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003718.5. 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
	CDK13	NM_003718.5	MANE Select	c.1066C>G	p.Pro356Ala	missense	Exon 1 of 14	NP_003709.3
	CDK13	NM_031267.3		c.1066C>G	p.Pro356Ala	missense	Exon 1 of 14	NP_112557.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK13	ENST00000181839.10	TSL:1 MANE Select	c.1066C>G	p.Pro356Ala	missense	Exon 1 of 14	ENSP00000181839.4
	CDK13	ENST00000340829.10	TSL:1	c.1066C>G	p.Pro356Ala	missense	Exon 1 of 14	ENSP00000340557.5
	CDK13	ENST00000646039.1		c.406C>G	p.Pro136Ala	missense	Exon 1 of 15	ENSP00000494168.1

Frequencies

GnomAD3 genomes AF: 0.00253 AC: 384 AN: 152014 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000652

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00210

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00443

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.00246 AC: 249 AN: 101338 AF XY: 0.00268

Gnomad AFR exome AF: 0.000297

Gnomad AMR exome AF: 0.00134

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00150

Gnomad NFE exome AF: 0.00410

Gnomad OTH exome AF: 0.00310

GnomAD4 exome AF: 0.00347 AC: 4574 AN: 1318952 Hom.: 14 Cov.: 33 AF XY: 0.00335 AC XY: 2175 AN XY: 648656

African (AFR) AF: 0.000556 AC: 15 AN: 26994

American (AMR) AF: 0.00181 AC: 43 AN: 23796

Ashkenazi Jewish (ASJ) AF: 0.0000526 AC: 1 AN: 19004

East Asian (EAS) AF: 0.0000304 AC: 1 AN: 32848

South Asian (SAS) AF: 0.000105 AC: 7 AN: 66968

European-Finnish (FIN) AF: 0.00183 AC: 67 AN: 36634

Middle Eastern (MID) AF: 0.000424 AC: 2 AN: 4722

European-Non Finnish (NFE) AF: 0.00407 AC: 4292 AN: 1053746

Other (OTH) AF: 0.00269 AC: 146 AN: 54240

GnomAD4 genome AF: 0.00252 AC: 384 AN: 152132 Hom.: 1 Cov.: 32 AF XY: 0.00235 AC XY: 175 AN XY: 74386

African (AFR) AF: 0.000650 AC: 27 AN: 41532

American (AMR) AF: 0.00209 AC: 32 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5126

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4818

European-Finnish (FIN) AF: 0.00188 AC: 20 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00443 AC: 301 AN: 67974

Other (OTH) AF: 0.00143 AC: 3 AN: 2104

Alfa AF: 0.00257 Hom.: 0

Bravo AF: 0.00290

ESP6500AA AF: 0.00129 AC: 4

ESP6500EA AF: 0.00258 AC: 17

ExAC AF: 0.00219 AC: 245

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	1	CDK13-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	12
DANN	Benign	0.93
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.62	T
M_CAP	Uncertain	0.26	D
MetaRNN	Benign	0.0063	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.21
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.054
Sift	Benign	0.14	T
Sift4G	Benign	0.082	T
Polyphen		0.0010	B
Vest4		0.051
MVP		0.40
MPC		0.14
ClinPred		0.025	T
GERP RS		2.3
PromoterAI		-0.052	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Varity_R		0.15
gMVP		0.090
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs17537669; hg19: chr7-39991306;