19-13927978-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_017721.5(CC2D1A):​c.2402C>T​(p.Thr801Met) variant causes a missense change. The variant allele was found at a frequency of 0.246 in 1,613,272 control chromosomes in the GnomAD database, including 52,801 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3521 hom., cov: 29)
Exomes 𝑓: 0.25 ( 49280 hom. )

Consequence

CC2D1A
NM_017721.5 missense

Scores

7
11

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 4.16
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 Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0016435385).
BP6
Variant 19-13927978-C-T is Benign according to our data. Variant chr19-13927978-C-T is described in ClinVar as [Benign]. Clinvar id is 128619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CC2D1ANM_017721.5 linkc.2402C>T p.Thr801Met missense_variant 23/29 ENST00000318003.11 NP_060191.3 Q6P1N0-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CC2D1AENST00000318003.11 linkc.2402C>T p.Thr801Met missense_variant 23/291 NM_017721.5 ENSP00000313601.6 Q6P1N0-1

Frequencies

GnomAD3 genomes
AF:
0.190
AC:
28790
AN:
151692
Hom.:
3522
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.0495
Gnomad AMI
AF:
0.496
Gnomad AMR
AF:
0.169
Gnomad ASJ
AF:
0.273
Gnomad EAS
AF:
0.0694
Gnomad SAS
AF:
0.162
Gnomad FIN
AF:
0.243
Gnomad MID
AF:
0.184
Gnomad NFE
AF:
0.274
Gnomad OTH
AF:
0.191
GnomAD3 exomes
AF:
0.210
AC:
52471
AN:
249330
Hom.:
6235
AF XY:
0.216
AC XY:
29179
AN XY:
135314
show subpopulations
Gnomad AFR exome
AF:
0.0434
Gnomad AMR exome
AF:
0.156
Gnomad ASJ exome
AF:
0.260
Gnomad EAS exome
AF:
0.0690
Gnomad SAS exome
AF:
0.173
Gnomad FIN exome
AF:
0.252
Gnomad NFE exome
AF:
0.269
Gnomad OTH exome
AF:
0.234
GnomAD4 exome
AF:
0.252
AC:
368728
AN:
1461462
Hom.:
49280
Cov.:
38
AF XY:
0.251
AC XY:
182399
AN XY:
727034
show subpopulations
Gnomad4 AFR exome
AF:
0.0376
Gnomad4 AMR exome
AF:
0.155
Gnomad4 ASJ exome
AF:
0.258
Gnomad4 EAS exome
AF:
0.0718
Gnomad4 SAS exome
AF:
0.174
Gnomad4 FIN exome
AF:
0.260
Gnomad4 NFE exome
AF:
0.276
Gnomad4 OTH exome
AF:
0.228
GnomAD4 genome
AF:
0.190
AC:
28783
AN:
151810
Hom.:
3521
Cov.:
29
AF XY:
0.186
AC XY:
13830
AN XY:
74164
show subpopulations
Gnomad4 AFR
AF:
0.0493
Gnomad4 AMR
AF:
0.169
Gnomad4 ASJ
AF:
0.273
Gnomad4 EAS
AF:
0.0690
Gnomad4 SAS
AF:
0.163
Gnomad4 FIN
AF:
0.243
Gnomad4 NFE
AF:
0.274
Gnomad4 OTH
AF:
0.189
Alfa
AF:
0.249
Hom.:
10261
Bravo
AF:
0.180
TwinsUK
AF:
0.281
AC:
1041
ALSPAC
AF:
0.295
AC:
1137
ESP6500AA
AF:
0.0438
AC:
181
ESP6500EA
AF:
0.267
AC:
2245
ExAC
AF:
0.209
AC:
25349
Asia WGS
AF:
0.106
AC:
371
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpFeb 01, 2024- -
not specified Benign:1
Likely benign, no assertion criteria providedclinical testingGenetic Services Laboratory, University of Chicago-Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitterclinical testingAmbry GeneticsMar 17, 2016This 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. -
Intellectual disability, autosomal recessive 3 Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabJul 14, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.067
BayesDel_addAF
Benign
-0.60
T
BayesDel_noAF
Benign
-0.49
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.075
T;.
Eigen
Uncertain
0.36
Eigen_PC
Uncertain
0.39
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.89
D;D
MetaRNN
Benign
0.0016
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.0
M;M
PrimateAI
Uncertain
0.62
T
PROVEAN
Benign
-2.0
N;.
REVEL
Benign
0.077
Sift
Benign
0.15
T;.
Sift4G
Benign
0.13
T;T
Polyphen
1.0
D;D
Vest4
0.19
MPC
0.77
ClinPred
0.023
T
GERP RS
5.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.067
gMVP
0.37

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: rs2305777; hg19: chr19-14038791; COSMIC: COSV54308018; COSMIC: COSV54308018; API