rs10410239

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_017721.5(CC2D1A):c.1281T>C(p.Gly427Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 1,611,382 control chromosomes in the GnomAD database, including 60,576 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 14790 hom., cov: 30)

Exomes 𝑓: 0.23 ( 45786 hom. )

Consequence

CC2D1A
NM_017721.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -3.31

Publications

16 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 19-13919876-T-C is Benign according to our data. Variant chr19-13919876-T-C is described in ClinVar as Benign. ClinVar VariationId is 128615.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.31 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CC2D1A	NM_017721.5 link	c.1281T>C	p.Gly427Gly	synonymous_variant	Exon 12 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.1281T>C	p.Gly427Gly	synonymous_variant	Exon 12 of 29	1	NM_017721.5	ENSP00000313601.6		Q6P1N0-1

Frequencies

GnomAD3 genomes

AF:

0.371

AC:

56173

AN:

151536

Hom.:

14735

Cov.:

show subpopulations

Gnomad AFR

AF:

0.745

Gnomad AMI

AF:

0.0890

Gnomad AMR

AF:

0.361

Gnomad ASJ

AF:

0.171

Gnomad EAS

AF:

0.309

Gnomad SAS

AF:

0.288

Gnomad FIN

AF:

0.153

Gnomad MID

AF:

0.168

Gnomad NFE

AF:

0.206

Gnomad OTH

AF:

0.322

GnomAD2 exomes

AF:

0.274

AC:

68267

AN:

249124

AF XY:

0.261

show subpopulations

Gnomad AFR exome

AF:

0.756

Gnomad AMR exome

AF:

0.367

Gnomad ASJ exome

AF:

0.181

Gnomad EAS exome

AF:

0.299

Gnomad FIN exome

AF:

0.168

Gnomad NFE exome

AF:

0.207

Gnomad OTH exome

AF:

0.256

GnomAD4 exome

AF:

0.231

AC:

337799

AN:

1459732

Hom.:

45786

Cov.:

AF XY:

0.230

AC XY:

167054

AN XY:

726136

show subpopulations

African (AFR)

AF:

0.768

AC:

25664

AN:

33416

American (AMR)

AF:

0.367

AC:

16397

AN:

44660

Ashkenazi Jewish (ASJ)

AF:

0.183

AC:

4786

AN:

26110

East Asian (EAS)

AF:

0.280

AC:

11092

AN:

39662

South Asian (SAS)

AF:

0.263

AC:

22667

AN:

86076

European-Finnish (FIN)

AF:

0.173

AC:

9244

AN:

53368

Middle Eastern (MID)

AF:

0.219

AC:

1140

AN:

5198

European-Non Finnish (NFE)

AF:

0.208

AC:

231600

AN:

1111024

Other (OTH)

AF:

0.253

AC:

15209

AN:

60218

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

11895

23789

35684

47578

59473

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8360

16720

25080

33440

41800

<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:

0.371

AC:

56292

AN:

151650

Hom.:

14790

Cov.:

AF XY:

0.367

AC XY:

27182

AN XY:

74118

show subpopulations

African (AFR)

AF:

0.746

AC:

30869

AN:

41380

American (AMR)

AF:

0.361

AC:

5489

AN:

15196

Ashkenazi Jewish (ASJ)

AF:

0.171

AC:

591

AN:

3462

East Asian (EAS)

AF:

0.309

AC:

1582

AN:

5118

South Asian (SAS)

AF:

0.287

AC:

1374

AN:

4794

European-Finnish (FIN)

AF:

0.153

AC:

1607

AN:

10530

Middle Eastern (MID)

AF:

0.180

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.206

AC:

13962

AN:

67874

Other (OTH)

AF:

0.327

AC:

684

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1359

2717

4076

5434

6793

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

474

948

1422

1896

2370

<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:

0.278

Hom.:

4718

Bravo

AF:

0.403

Asia WGS

AF:

0.372

AC:

1290

AN:

3478

EpiCase

AF:

0.205

EpiControl

AF:

0.202

ClinVar

Significance: Benign

Submissions summary: Benign:4

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 11, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.59

(source)

DANN

Benign

0.47

PhyloP100

-3.3

PromoterAI

-0.0040

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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