chr19-13927978-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Clinical Significance

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

Conservation

PhyloP100: 4.16

Publications

32 publications found

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]

CC2D1A Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
intellectual disability, autosomal recessive 3
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
autosomal recessive non-syndromic intellectual disability
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CC2D1A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 CliVar as Benign. Clinvar id is 128619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-13927978-C-T is described in CliVar as Benign. Clinvar id is 128619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-13927978-C-T is described in CliVar as Benign. Clinvar id is 128619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-13927978-C-T is described in CliVar as Benign. Clinvar id is 128619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-13927978-C-T is described in CliVar as Benign. Clinvar id is 128619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-13927978-C-T is described in CliVar as Benign. Clinvar id is 128619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-13927978-C-T is described in CliVar as Benign. Clinvar id is 128619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-13927978-C-T is described in CliVar as Benign. Clinvar id is 128619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-13927978-C-T is described in CliVar as Benign. Clinvar id is 128619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-13927978-C-T is described in CliVar as Benign. Clinvar id is 128619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-13927978-C-T is described in CliVar as Benign. Clinvar id is 128619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-13927978-C-T is described in CliVar as Benign. Clinvar id is 128619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-13927978-C-T is described in CliVar as Benign. Clinvar id is 128619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-13927978-C-T is described in CliVar as Benign. Clinvar id is 128619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-13927978-C-T is described in CliVar as Benign. Clinvar id is 128619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-13927978-C-T is described in CliVar as Benign. Clinvar id is 128619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-13927978-C-T is described in CliVar as Benign. Clinvar id is 128619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-13927978-C-T is described in CliVar as Benign. Clinvar id is 128619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-13927978-C-T is described in CliVar as Benign. Clinvar id is 128619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-13927978-C-T is described in CliVar as Benign. Clinvar id is 128619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-13927978-C-T is described in CliVar as Benign. Clinvar id is 128619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-13927978-C-T is described in CliVar as Benign. Clinvar id is 128619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-13927978-C-T is described in CliVar as Benign. Clinvar id is 128619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-13927978-C-T is described in CliVar as Benign. Clinvar id is 128619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-13927978-C-T is described in CliVar as Benign. Clinvar id is 128619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-13927978-C-T is described in CliVar as Benign. Clinvar id is 128619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-13927978-C-T is described in CliVar as Benign. Clinvar id is 128619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-13927978-C-T is described in CliVar as Benign. Clinvar id is 128619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-13927978-C-T is described in CliVar as Benign. Clinvar id is 128619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-13927978-C-T is described in CliVar as Benign. Clinvar id is 128619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-13927978-C-T is described in CliVar 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 rank	MANE	Protein	UniProt
CC2D1A	NM_017721.5 link	c.2402C>T	p.Thr801Met	missense_variant	Exon 23 of 29	ENST00000318003.11	NP_060191.3	Q6P1N0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CC2D1A	ENST00000318003.11 link	c.2402C>T	p.Thr801Met	missense_variant	Exon 23 of 29	1	NM_017721.5	ENSP00000313601.6		Q6P1N0-1

Frequencies

GnomAD3 genomes

AF:

0.190

AC:

28790

AN:

151692

Hom.:

3522

Cov.:

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

GnomAD2 exomes

AF:

0.210

AC:

52471

AN:

249330

AF XY:

0.216

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 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.:

AF XY:

0.251

AC XY:

182399

AN XY:

727034

show subpopulations

African (AFR)

AF:

0.0376

AC:

1260

AN:

33478

American (AMR)

AF:

0.155

AC:

6938

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.258

AC:

6755

AN:

26134

East Asian (EAS)

AF:

0.0718

AC:

2850

AN:

39698

South Asian (SAS)

AF:

0.174

AC:

14976

AN:

86246

European-Finnish (FIN)

AF:

0.260

AC:

13818

AN:

53202

Middle Eastern (MID)

AF:

0.185

AC:

1067

AN:

5768

European-Non Finnish (NFE)

AF:

0.276

AC:

307299

AN:

1111824

Other (OTH)

AF:

0.228

AC:

13765

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

15082

30164

45245

60327

75409

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10022

20044

30066

40088

50110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.190

AC:

28783

AN:

151810

Hom.:

3521

Cov.:

AF XY:

0.186

AC XY:

13830

AN XY:

74164

show subpopulations

African (AFR)

AF:

0.0493

AC:

2046

AN:

41468

American (AMR)

AF:

0.169

AC:

2573

AN:

15232

Ashkenazi Jewish (ASJ)

AF:

0.273

AC:

948

AN:

3470

East Asian (EAS)

AF:

0.0690

AC:

355

AN:

5148

South Asian (SAS)

AF:

0.163

AC:

782

AN:

4810

European-Finnish (FIN)

AF:

0.243

AC:

2547

AN:

10494

Middle Eastern (MID)

AF:

0.184

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.274

AC:

18632

AN:

67886

Other (OTH)

AF:

0.189

AC:

397

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1077

2154

3231

4308

5385

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

316

632

948

1264

1580

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.240

Hom.:

19945

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

Mar 17, 2016

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Intellectual disability, autosomal recessive 3

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.49

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.075

T;.

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.89

D;D

MetaRNN

Benign

0.0016

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

M;M

PhyloP100

4.2

PrimateAI

Uncertain

0.62

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

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.067

gMVP

0.37

Mutation Taster

=94/6

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over