rs1057520196
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_030653.4(DDX11):āc.1523T>Gā(p.Leu508Arg) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000682 in 1,613,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_030653.4 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DDX11 | NM_030653.4 | c.1523T>G | p.Leu508Arg | missense_variant, splice_region_variant | 16/27 | ENST00000542838.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DDX11 | ENST00000542838.6 | c.1523T>G | p.Leu508Arg | missense_variant, splice_region_variant | 16/27 | 1 | NM_030653.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152178Hom.: 0 Cov.: 31
GnomAD4 exome AF: 0.00000684 AC: 10AN: 1460956Hom.: 0 Cov.: 34 AF XY: 0.00000550 AC XY: 4AN XY: 726826
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152178Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74336
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 30, 2020 | The c.1523T>G (p.L508R) alteration is located in exon 16 (coding exon 15) of the DDX11 gene. This alteration results from a T to G substitution at nucleotide position 1523, causing the leucine (L) at amino acid position 508 to be replaced by an arginine (R). Based on data from the Genome Aggregation Database (gnomAD), the DDX11 c.1523T>G alteration was not observed, with coverage at this position. The c.1523T>G alteration in DDX11 was previously detected in trans with c.1949-1G>A in two sisters with Warsaw breakage syndrome via clinical exome sequencing of the proband and parents. Both sisters were reported to have pre- and postnatal growth restriction, microcephaly, intellectual disability, sensorineural hearing loss with cochlear abnormalities, and facial dysmorphic features. In addition, the sisters had early menarche at 8 and 10 years of age, bilateral small thumbs, and the younger, more severely affected sister had small fibulae. Both sisters also showed a small increase in spontaneous and DEB-induced chromosome breaks that were not consistent with Fanconi anemia (Eppley, 2017). The p.L508 amino acid is conserved in available vertebrate species. The in silico prediction for the p.L508R alteration is inconclusive. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Aug 26, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at