7-39950686-G-C

Variant names:

• chr7-39950686-G-C
• rs1215693519
• NM_003718.5:c.45G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_003718.5(CDK13):​c.45G>C​(p.Leu15Leu) variant causes a synonymous change. The variant allele was found at a frequency of 0.00000785 in 1,273,602 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L15L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000079 (0 hom.)
• Consequence: CDK13 NM_003718.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.73
• Publications: 1 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BS1: Variant frequency is greater than expected in population eas. GnomAdExome4 allele frequency = 0.00000785 (10/1273602) while in subpopulation EAS AF = 0.000286 (8/27962). AF 95% confidence interval is 0.000142. There are 0 homozygotes in GnomAdExome4. There are 2 alleles in the male GnomAdExome4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK13	NM_003718.5	c.45G>C	p.Leu15Leu	synonymous_variant	Exon 1 of 14	ENST00000181839.10	NP_003709.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK13	ENST00000181839.10	c.45G>C	p.Leu15Leu	synonymous_variant	Exon 1 of 14	1	NM_003718.5	ENSP00000181839.4
CDK13	ENST00000340829.10	c.45G>C	p.Leu15Leu	synonymous_variant	Exon 1 of 14	1		ENSP00000340557.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000785 AC: 10 AN: 1273602 Hom.: 0 Cov.: 33 AF XY: 0.00000321 AC XY: 2 AN XY: 623828

African (AFR) AF: 0.00 AC: 0 AN: 25578

American (AMR) AF: 0.00 AC: 0 AN: 19312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20236

East Asian (EAS) AF: 0.000286 AC: 8 AN: 27962

South Asian (SAS) AF: 0.00 AC: 0 AN: 64442

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32800

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3736

European-Non Finnish (NFE) AF: 0.00000195 AC: 2 AN: 1026828

Other (OTH) AF: 0.00 AC: 0 AN: 52708

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

Asia WGS AF: 0.000289 AC: 1 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	13
DANN	Benign	0.93
PhyloP100		4.7
PromoterAI		-0.059	Neutral

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: rs1215693519; hg19: chr7-39990285;