rs149910292
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001286577.2(C2CD3):c.704C>T(p.Pro235Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00556 in 1,604,348 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P235P) has been classified as Likely benign.
Frequency
Consequence
NM_001286577.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
C2CD3 | NM_001286577.2 | c.704C>T | p.Pro235Leu | missense_variant | 4/33 | ENST00000334126.12 | |
C2CD3 | NM_015531.6 | c.704C>T | p.Pro235Leu | missense_variant | 4/31 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
C2CD3 | ENST00000334126.12 | c.704C>T | p.Pro235Leu | missense_variant | 4/33 | 5 | NM_001286577.2 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.00362 AC: 550AN: 152136Hom.: 3 Cov.: 32
GnomAD3 exomes AF: 0.00364 AC: 915AN: 251392Hom.: 1 AF XY: 0.00343 AC XY: 466AN XY: 135876
GnomAD4 exome AF: 0.00577 AC: 8374AN: 1452094Hom.: 26 Cov.: 30 AF XY: 0.00542 AC XY: 3921AN XY: 723086
GnomAD4 genome ? AF: 0.00361 AC: 549AN: 152254Hom.: 3 Cov.: 32 AF XY: 0.00313 AC XY: 233AN XY: 74442
ClinVar
Submissions by phenotype
not provided Benign:4
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Dec 01, 2023 | C2CD3: BP4, BS2 - |
Likely benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Orofaciodigital syndrome type 14 Benign:2
Benign, criteria provided, single submitter | clinical testing | Daryl Scott Lab, Baylor College of Medicine | Nov 10, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Centre for Mendelian Genomics, University Medical Centre Ljubljana | Nov 08, 2018 | This variant was classified as: Benign. The following ACMG criteria were applied in classifying this variant: BS1,BS2. - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital | May 16, 2017 | BS1, BS2; This alteration has an allele frequency that is greater than expected for the associated disease, and was seen in a healthy adult where full penetrance of the disorder is expected at an early age. - |
C2CD3-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 27, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 03, 2021 | 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at