rs536646769
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_001378615.1(CC2D2A):āc.576T>Cā(p.Tyr192=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000881 in 1,600,266 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 (ā ā ).
Frequency
Genomes: š 0.000013 ( 0 hom., cov: 32)
Exomes š: 0.000096 ( 0 hom. )
Consequence
CC2D2A
NM_001378615.1 synonymous
NM_001378615.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.204
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 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=-0.57).
BP6
?
Variant 4-15511282-T-C is Benign according to our data. Variant chr4-15511282-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 215779.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.204 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CC2D2A | NM_001378615.1 | c.576T>C | p.Tyr192= | synonymous_variant | 8/37 | ENST00000424120.6 | |
LOC124900672 | XR_007058062.1 | n.253-3172A>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CC2D2A | ENST00000424120.6 | c.576T>C | p.Tyr192= | synonymous_variant | 8/37 | 5 | NM_001378615.1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152208Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000391 AC: 9AN: 230438Hom.: 0 AF XY: 0.0000480 AC XY: 6AN XY: 124888
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GnomAD4 exome AF: 0.0000960 AC: 139AN: 1447940Hom.: 0 Cov.: 30 AF XY: 0.0000945 AC XY: 68AN XY: 719466
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152326Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74488
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Meckel-Gruber syndrome;C0431399:Familial aplasia of the vermis Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 07, 2023 | - - |
CC2D2A-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 04, 2021 | 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). - |
Computational scores
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Name
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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