rs199945435
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_001378615.1(CC2D2A):c.*1T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000591 in 1,455,908 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00041 ( 1 hom., cov: 33)
Exomes 𝑓: 0.00061 ( 0 hom. )
Consequence
CC2D2A
NM_001378615.1 3_prime_UTR
NM_001378615.1 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.128
Genes affected
CC2D2A (HGNC:29253): (coiled-coil and C2 domain containing 2A) This gene encodes a coiled-coil and calcium binding domain protein that appears to play a critical role in cilia formation. Mutations in this gene cause Meckel syndrome type 6, as well as Joubert syndrome type 9. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP6
Variant 4-15601426-T-A is Benign according to our data. Variant chr4-15601426-T-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 257381.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=4}.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| CC2D2A | NM_001378615.1 | c.*1T>A | 3_prime_UTR_variant | 37/37 | ENST00000424120.6 | NP_001365544.1 | ||
| CC2D2A | NM_001080522.2 | c.*1T>A | 3_prime_UTR_variant | 38/38 | NP_001073991.2 | |||
| CC2D2A | NM_001378617.1 | c.*1T>A | 3_prime_UTR_variant | 35/35 | NP_001365546.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| CC2D2A | ENST00000424120.6 | c.*1T>A | 3_prime_UTR_variant | 37/37 | 5 | NM_001378615.1 | ENSP00000403465 | P1 |
Frequencies
GnomAD3 genomes 0.000407 AC: 62AN: 152200Hom.: 1 Cov.: 33
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GnomAD3 exomes AF: 0.000446 AC: 59AN: 132364Hom.: 0 AF XY: 0.000538 AC XY: 38AN XY: 70588
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GnomAD4 exome AF: 0.000612 AC: 798AN: 1303590Hom.: 0 Cov.: 30 AF XY: 0.000594 AC XY: 377AN XY: 635102
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GnomAD4 genome 0.000407 AC: 62AN: 152318Hom.: 1 Cov.: 33 AF XY: 0.000389 AC XY: 29AN XY: 74480
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:4Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:1
| Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 28, 2023 | See Variant Classification Assertion Criteria. - |
| Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jul 14, 2020 | - - |
Meckel syndrome, type 6 Uncertain:1
| Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Joubert syndrome 9 Uncertain:1
| Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
CC2D2A-related disorder Uncertain:1
| Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
not specified Benign:1
| Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at