rs200848845
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_017721.5(CC2D1A):āc.2731C>Gā(p.Arg911Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000298 in 1,611,688 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 Uncertain significance (ā ā ).
Frequency
Genomes: š 0.000099 ( 0 hom., cov: 32)
Exomes š: 0.000023 ( 0 hom. )
Consequence
CC2D1A
NM_017721.5 missense
NM_017721.5 missense
Scores
7
12
Clinical Significance
Conservation
PhyloP100: 0.179
Genes affected
CC2D1A (HGNC:30237): (coiled-coil and C2 domain containing 1A) This gene encodes a transcriptional repressor that binds to a conserved 14-bp 5'-repressor element and regulates expression of the 5-hydroxytryptamine (serotonin) receptor 1A gene in neuronal cells. The DNA binding and transcriptional repressor activities of the protein are inhibited by calcium. A mutation in this gene results in a nonsyndromic form of cognitive disability (MRT3). [provided by RefSeq, Jul 2017]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.11624676).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CC2D1A | NM_017721.5 | c.2731C>G | p.Arg911Gly | missense_variant | 27/29 | ENST00000318003.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CC2D1A | ENST00000318003.11 | c.2731C>G | p.Arg911Gly | missense_variant | 27/29 | 1 | NM_017721.5 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000986 AC: 15AN: 152070Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000574 AC: 14AN: 243946Hom.: 0 AF XY: 0.0000598 AC XY: 8AN XY: 133670
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GnomAD4 exome AF: 0.0000226 AC: 33AN: 1459618Hom.: 0 Cov.: 33 AF XY: 0.0000165 AC XY: 12AN XY: 726178
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GnomAD4 genome ? AF: 0.0000986 AC: 15AN: 152070Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74272
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jan 29, 2017 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 16, 2016 | The p.R911G variant (also known as c.2731C>G), located in coding exon 27 of the CC2D1A gene, results from a C to G substitution at nucleotide position 2731. The arginine at codon 911 is replaced by glycine, an amino acid with dissimilar properties. This variant was previously reported in the SNPDatabase as rs200848845. Based on data from the NHLBI Exome Sequencing Project (ESP), the G allele has an overall frequency of approximately 0.01% (1/12186) total alleles studied, having been observed in 0.03% (1/3922) African American alleles. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
N;.
REVEL
Benign
Sift
Uncertain
D;.
Sift4G
Uncertain
D;D
Polyphen
P;P
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
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