rs372549709
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001080463.2(DYNC2H1):c.5152-3A>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000533 in 1,480,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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 (★).
Frequency
Consequence
NM_001080463.2 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DYNC2H1 | NM_001080463.2 | c.5152-3A>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000650373.2 | |||
DYNC2H1 | NM_001377.3 | c.5152-3A>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000375735.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DYNC2H1 | ENST00000375735.7 | c.5152-3A>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_001377.3 | P3 | |||
DYNC2H1 | ENST00000650373.2 | c.5152-3A>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | NM_001080463.2 | A1 | ||||
DYNC2H1 | ENST00000334267.11 | c.2205+36464A>C | intron_variant | 1 | |||||
DYNC2H1 | ENST00000649323.1 | c.*2697-3A>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152130Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000743 AC: 15AN: 201768Hom.: 0 AF XY: 0.0000909 AC XY: 10AN XY: 109958
GnomAD4 exome AF: 0.0000542 AC: 72AN: 1328668Hom.: 0 Cov.: 30 AF XY: 0.0000722 AC XY: 47AN XY: 650770
GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152130Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74316
ClinVar
Submissions by phenotype
Jeune thoracic dystrophy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 19, 2022 | This sequence change falls in intron 33 of the DYNC2H1 gene. It does not directly change the encoded amino acid sequence of the DYNC2H1 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs372549709, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with DYNC2H1-related conditions. ClinVar contains an entry for this variant (Variation ID: 407164). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at