rs431905519
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Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PVS1_ModeratePM2PP5
The NM_052844.4(DYNC2I2):c.1541_1542del(p.Thr514ArgfsTer11) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000806 in 1,613,458 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000055 ( 0 hom. )
Consequence
DYNC2I2
NM_052844.4 frameshift
NM_052844.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.61
Genes affected
DYNC2I2 (HGNC:28296): (dynein 2 intermediate chain 2) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. Defects in this gene are a cause of short-rib thoracic dysplasia 11 with or without polydactyly. [provided by RefSeq, Mar 2014]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0435 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 9-128633812-CTG-C is Pathogenic according to our data. Variant chr9-128633812-CTG-C is described in ClinVar as [Pathogenic]. Clinvar id is 97043.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DYNC2I2 | NM_052844.4 | c.1541_1542del | p.Thr514ArgfsTer11 | frameshift_variant | 9/9 | ENST00000372715.7 | |
DYNC2I2 | XM_011519179.3 | c.1457_1458del | p.Thr486ArgfsTer11 | frameshift_variant | 10/10 | ||
DYNC2I2 | XM_047424057.1 | c.1541_1542del | p.Thr514ArgfsTer11 | frameshift_variant | 10/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DYNC2I2 | ENST00000372715.7 | c.1541_1542del | p.Thr514ArgfsTer11 | frameshift_variant | 9/9 | 1 | NM_052844.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000328 AC: 5AN: 152234Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250912Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135804
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GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461224Hom.: 0 AF XY: 0.00000688 AC XY: 5AN XY: 726934
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GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152234Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74368
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Short-rib thoracic dysplasia 11 with or without polydactyly Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 07, 2013 | - - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at