rs75601897
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_017721.5(CC2D1A):āc.1634T>Cā(p.Ile545Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00123 in 1,612,160 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.0070 ( 7 hom., cov: 32)
Exomes š: 0.00063 ( 9 hom. )
Consequence
CC2D1A
NM_017721.5 missense
NM_017721.5 missense
Scores
2
8
8
Clinical Significance
Conservation
PhyloP100: 7.31
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 Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0063429177).
BP6
?
Variant 19-13920915-T-C is Benign according to our data. Variant chr19-13920915-T-C is described in ClinVar as [Benign]. Clinvar id is 128617.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00702 (1070/152368) while in subpopulation AFR AF= 0.0247 (1028/41590). AF 95% confidence interval is 0.0235. There are 7 homozygotes in gnomad4. There are 508 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 7 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CC2D1A | NM_017721.5 | c.1634T>C | p.Ile545Thr | missense_variant | 14/29 | ENST00000318003.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CC2D1A | ENST00000318003.11 | c.1634T>C | p.Ile545Thr | missense_variant | 14/29 | 1 | NM_017721.5 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.00703 AC: 1071AN: 152250Hom.: 7 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00170 AC: 415AN: 243750Hom.: 4 AF XY: 0.00128 AC XY: 170AN XY: 132656
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GnomAD4 exome AF: 0.000630 AC: 919AN: 1459792Hom.: 9 Cov.: 33 AF XY: 0.000552 AC XY: 401AN XY: 726116
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GnomAD4 genome ? AF: 0.00702 AC: 1070AN: 152368Hom.: 7 Cov.: 32 AF XY: 0.00682 AC XY: 508AN XY: 74512
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ESP6500AA
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256
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jul 08, 2013 | - - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 08, 2016 | This alteration is classified as 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. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.
REVEL
Benign
Sift
Benign
T;.
Sift4G
Uncertain
D;D
Polyphen
D;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