chr4-15596177-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP5BP4
The NM_001378615.1(CC2D2A):c.4407C>G(p.Ser1469Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000258 in 1,547,426 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. S1469S) has been classified as Likely benign.
Frequency
Consequence
NM_001378615.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CC2D2A | NM_001378615.1 | c.4407C>G | p.Ser1469Arg | missense_variant | 34/37 | ENST00000424120.6 | |
CC2D2A | NM_001080522.2 | c.4407C>G | p.Ser1469Arg | missense_variant | 35/38 | ||
CC2D2A | NM_001378617.1 | c.4260C>G | p.Ser1420Arg | missense_variant | 32/35 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CC2D2A | ENST00000424120.6 | c.4407C>G | p.Ser1469Arg | missense_variant | 34/37 | 5 | NM_001378615.1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152198Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000320 AC: 5AN: 156244Hom.: 0 AF XY: 0.0000363 AC XY: 3AN XY: 82602
GnomAD4 exome AF: 0.0000272 AC: 38AN: 1395228Hom.: 0 Cov.: 29 AF XY: 0.0000305 AC XY: 21AN XY: 688140
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152198Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74358
ClinVar
Submissions by phenotype
Meckel-Gruber syndrome Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Oct 29, 2013 | - - |
Meckel-Gruber syndrome;C0431399:Familial aplasia of the vermis Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 25, 2022 | This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 1469 of the CC2D2A protein (p.Ser1469Arg). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with clinical features of Joubert syndrome (Invitae). ClinVar contains an entry for this variant (Variation ID: 126245). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CC2D2A protein function. 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