rs376443152

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_017721.5(CC2D1A):c.2707C>T(p.Arg903Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000185 in 1,294,950 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R903Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00031 ( 0 hom., cov: 14)

Exomes 𝑓: 0.00018 ( 3 hom. )

Consequence

CC2D1A
NM_017721.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:3

Conservation

PhyloP100: -0.921

Publications

1 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: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08847353).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017721.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CC2D1A	NM_017721.5	MANE Select	c.2707C>T	p.Arg903Trp	missense	Exon 26 of 29	NP_060191.3
	CC2D1A	NM_001411138.1		c.2704C>T	p.Arg902Trp	missense	Exon 26 of 29	NP_001398067.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CC2D1A	ENST00000318003.11	TSL:1 MANE Select	c.2707C>T	p.Arg903Trp	missense	Exon 26 of 29	ENSP00000313601.6
CC2D1A	ENST00000589606.5	TSL:1	c.2704C>T	p.Arg902Trp	missense	Exon 26 of 29	ENSP00000467526.1
CC2D1A	ENST00000586955.5	TSL:1	n.*974C>T		non_coding_transcript_exon	Exon 21 of 24	ENSP00000465376.1

Frequencies

GnomAD3 genomes

AF:

0.000314

AC:

AN:

79622

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000156

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000781

Gnomad ASJ

AF:

0.00135

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000973

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000293

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000308

AC:

AN:

126696

AF XY:

0.000361

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000329

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000203

Gnomad NFE exome

AF:

0.000221

Gnomad OTH exome

AF:

0.000907

GnomAD4 exome

AF:

0.000177

AC:

215

AN:

1215294

Hom.:

Cov.:

AF XY:

0.000193

AC XY:

115

AN XY:

594620

show subpopulations

African (AFR)

AF:

0.0000367

AC:

AN:

27250

American (AMR)

AF:

0.000203

AC:

AN:

29628

Ashkenazi Jewish (ASJ)

AF:

0.000574

AC:

AN:

19160

East Asian (EAS)

AF:

0.0000425

AC:

AN:

23554

South Asian (SAS)

AF:

0.000599

AC:

AN:

68406

European-Finnish (FIN)

AF:

0.000146

AC:

AN:

34266

Middle Eastern (MID)

AF:

0.00234

AC:

AN:

4698

European-Non Finnish (NFE)

AF:

0.000129

AC:

124

AN:

961692

Other (OTH)

AF:

0.000322

AC:

AN:

46640

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.000314

AC:

AN:

79656

Hom.:

Cov.:

AF XY:

0.000217

AC XY:

AN XY:

36926

show subpopulations

African (AFR)

AF:

0.000155

AC:

AN:

19344

American (AMR)

AF:

0.000779

AC:

AN:

6420

Ashkenazi Jewish (ASJ)

AF:

0.00135

AC:

AN:

2218

East Asian (EAS)

AF:

0.00

AC:

AN:

2964

South Asian (SAS)

AF:

0.000980

AC:

AN:

2040

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3966

Middle Eastern (MID)

AF:

0.00

AC:

AN:

170

European-Non Finnish (NFE)

AF:

0.000293

AC:

AN:

40946

Other (OTH)

AF:

0.00

AC:

AN:

1028

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.537

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000278

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000123

AC:

ExAC

AF:

0.000169

AC:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Intellectual disability, autosomal recessive 3 (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.082

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.23

LIST_S2

Uncertain

0.91

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.088

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

PhyloP100

-0.92

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-2.0

REVEL

Benign

0.15

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.012

Polyphen

1.0

Vest4

0.48

MVP

0.39

MPC

0.64

ClinPred

0.064

GERP RS

0.37

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Varity_R

0.096

gMVP

0.33

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over