18-53526713-C-CTGAAG
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_ModeratePM2
The NM_005215.4(DCC):c.4211_4215dupAAGTG(p.Ser1406LysfsTer22) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_005215.4 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:1
Identified as heterozygous in four family members affected with congenital mirror movements and one asymptomatic carrier (PMID: 29366874); Frameshift variant predicted to result in abnormal protein length as the last 42 amino acids are replaced with 21 different amino acids; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 29366874, 31697046) -
DCC-related disorder Uncertain:1
The DCC c.4211_4215dup5 variant is predicted to result in a frameshift and premature protein termination (p.Ser1406Lysfs*22). This variant was reported to segregate with the disease in four of five individuals from a family with congenital mirror movements (Bierhals T et al. 2018. PubMed ID: 29366874). This truncating variant occurs in the 3' end of penultimate exon and is predicted to escape from nonsense-mediated mRNA decay. This variant has not been reported in a large population database, indicating this variant is rare. Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.