rs765282375

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6

The ENST00000318003.11(CC2D1A):​c.959C>A​(p.Pro320Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000107 in 1,612,276 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00021 ( 1 hom., cov: 33)
Exomes 𝑓: 0.000096 ( 0 hom. )

Consequence

CC2D1A
ENST00000318003.11 missense

Scores

19

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 0.529
Variant links:
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 Likely_benign. Variant got -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.006571442).
BP6
Variant 19-13918758-C-A is Benign according to our data. Variant chr19-13918758-C-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 434598.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=2}.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CC2D1ANM_017721.5 linkuse as main transcriptc.959C>A p.Pro320Gln missense_variant 9/29 ENST00000318003.11 NP_060191.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CC2D1AENST00000318003.11 linkuse as main transcriptc.959C>A p.Pro320Gln missense_variant 9/291 NM_017721.5 ENSP00000313601 P3Q6P1N0-1

Frequencies

GnomAD3 genomes
AF:
0.000210
AC:
32
AN:
152186
Hom.:
1
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000458
Gnomad ASJ
AF:
0.00518
Gnomad EAS
AF:
0.000964
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000158
AC:
39
AN:
247050
Hom.:
0
AF XY:
0.000149
AC XY:
20
AN XY:
134058
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000874
Gnomad ASJ exome
AF:
0.00303
Gnomad EAS exome
AF:
0.000278
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000895
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000959
AC:
140
AN:
1459972
Hom.:
0
Cov.:
33
AF XY:
0.0000950
AC XY:
69
AN XY:
726180
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000673
Gnomad4 ASJ exome
AF:
0.00327
Gnomad4 EAS exome
AF:
0.000453
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000162
Gnomad4 OTH exome
AF:
0.000232
GnomAD4 genome
AF:
0.000210
AC:
32
AN:
152304
Hom.:
1
Cov.:
33
AF XY:
0.000255
AC XY:
19
AN XY:
74474
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000458
Gnomad4 ASJ
AF:
0.00518
Gnomad4 EAS
AF:
0.000966
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000226
Hom.:
0
Bravo
AF:
0.000155
ExAC
AF:
0.000124
AC:
15

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingGenetic Services Laboratory, University of ChicagoMar 17, 2016- -
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsSep 27, 2022This alteration is classified as likely 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
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 25, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.076
BayesDel_addAF
Benign
-0.42
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
16
DANN
Benign
0.92
DEOGEN2
Benign
0.081
T;.
Eigen
Benign
-0.77
Eigen_PC
Benign
-0.74
FATHMM_MKL
Benign
0.012
N
LIST_S2
Benign
0.55
T;T
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.0066
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.69
N;N
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.29
T
PROVEAN
Benign
-0.40
N;.
REVEL
Benign
0.055
Sift
Benign
0.17
T;.
Sift4G
Benign
0.15
T;T
Polyphen
0.0
B;B
Vest4
0.099
MutPred
0.29
Loss of glycosylation at P320 (P = 0.0044);Loss of glycosylation at P320 (P = 0.0044);
MVP
0.46
MPC
0.20
ClinPred
0.028
T
GERP RS
1.4
Varity_R
0.037
gMVP
0.11

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.11
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs765282375; hg19: chr19-14029571; API