9-128633804-C-T
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_052844.4(DYNC2I2):c.1551G>A(p.Thr517=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000831 in 1,613,476 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000088 ( 0 hom. )
Consequence
DYNC2I2
NM_052844.4 synonymous
NM_052844.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.42
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 Benign. Variant got -11 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.64).
BP6
?
Variant 9-128633804-C-T is Benign according to our data. Variant chr9-128633804-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1681166.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-3.42 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DYNC2I2 | NM_052844.4 | c.1551G>A | p.Thr517= | synonymous_variant | 9/9 | ENST00000372715.7 | |
DYNC2I2 | XM_047424057.1 | c.1551G>A | p.Thr517= | synonymous_variant | 10/10 | ||
DYNC2I2 | XM_011519179.3 | c.1467G>A | p.Thr489= | synonymous_variant | 10/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DYNC2I2 | ENST00000372715.7 | c.1551G>A | p.Thr517= | synonymous_variant | 9/9 | 1 | NM_052844.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000328 AC: 5AN: 152214Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000155 AC: 39AN: 251056Hom.: 0 AF XY: 0.000133 AC XY: 18AN XY: 135840
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GnomAD4 exome AF: 0.0000883 AC: 129AN: 1461262Hom.: 0 Cov.: 32 AF XY: 0.0000977 AC XY: 71AN XY: 726950
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GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152214Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74366
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 13, 2024 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Short-rib thoracic dysplasia 11 with or without polydactyly Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Aug 10, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at