Submissions for variant NM_003718.5(CDK13):c.2638C>T (p.Arg880Cys)

dbSNP: rs1005618432

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München	RCV001254124	SCV001430064	likely pathogenic	Congenital heart defects, dysmorphic facial features, and intellectual developmental disorder	2020-05-20	criteria provided, single submitter	clinical testing
Genetics Laboratory, UDIAT-Centre Diagnòstic, Hospital Universitari Parc Tauli	RCV001254124	SCV002577685	pathogenic	Congenital heart defects, dysmorphic facial features, and intellectual developmental disorder	2022-10-04	criteria provided, single submitter	clinical testing	PS1;PM1;PM2_supporting;PM6;PP2;PP3
Ambry Genetics	RCV002568737	SCV003602117	likely pathogenic	Inborn genetic diseases	2022-02-10	criteria provided, single submitter	clinical testing	The c.2638C>T (p.R880C) alteration is located in exon 8 (coding exon 8) of the CDK13 gene. This alteration results from a C to T substitution at nucleotide position 2638, causing the arginine (R) at amino acid position 880 to be replaced by a cysteine (C). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This alteration was reported de novo in an individual with feeding problems, borderline intellectual disability, behavioral problems, hypotonia, sleep problems, periventricular leukodystrophy, dysmorphic facial features (including blepharophimosis, strabismus, hypertelorism, large mouth, flat midface, upslanting palpebral fissures, short nose, epicanthal folds, and flared eyebrows), gynecomastia, sloping shoulders, inverted nipples, tapered fingers, fetal pads, pes planus, café au lait spots, metabolic abnormalities, and muscle biopsy with many type I fibers and small type II fibers (van den Akker, 2018). This amino acid position is highly conserved in available vertebrate species. This missense alteration is located in a region that has a low rate of benign missense variation (Lek, 2016; Firth, 2009). The in silico prediction for this alteration is inconclusive. Based on the available evidence, this alteration is classified as likely pathogenic.
3billion	RCV001254124	SCV003841301	pathogenic	Congenital heart defects, dysmorphic facial features, and intellectual developmental disorder	2023-02-23	criteria provided, single submitter	clinical testing	The variant is not observed in the gnomAD v2.1.1 dataset. Missense changes are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.68; 3Cnet: 0.96). Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000976738). The variant has been previously reported as de novo in a similarly affected individual (PMID: 29393965). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.
GeneDx	RCV001529484	SCV003918484	pathogenic	not provided	2022-10-12	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 29393965)
CeGaT Center for Human Genetics Tuebingen	RCV001529484	SCV004010665	pathogenic	not provided	2023-06-01	criteria provided, single submitter	clinical testing	CDK13: PS2, PM1, PM2, PS4:Moderate, PP2
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001529484	SCV001743024	pathogenic	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV001529484	SCV001809532	pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001529484	SCV001953371	pathogenic	not provided		no assertion criteria provided	clinical testing