10-277431-A-C
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate
The NM_014974.3(DIP2C):c.4565T>G(p.Ile1522Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000929 in 1,613,976 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. I1522I) has been classified as Likely benign.
Frequency
Consequence
NM_014974.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DIP2C | NM_014974.3 | c.4565T>G | p.Ile1522Ser | missense_variant | 37/37 | ENST00000280886.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DIP2C | ENST00000280886.12 | c.4565T>G | p.Ile1522Ser | missense_variant | 37/37 | 1 | NM_014974.3 | P1 | |
DIP2C | ENST00000634311.1 | c.4763T>G | p.Ile1588Ser | missense_variant | 39/39 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 152084Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251460Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135910
GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461892Hom.: 0 Cov.: 32 AF XY: 0.0000110 AC XY: 8AN XY: 727246
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 152084Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74300
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 28, 2024 | This sequence change replaces isoleucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1522 of the DIP2C protein (p.Ile1522Ser). This variant is present in population databases (rs764302365, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with DIP2C-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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