Genetic Variant CC2D1A:n.*1516G>A (chr19-13930788-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000586955.5(CC2D1A):n.*1516G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 271,318 control chromosomes in the GnomAD database, including 3,524 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.15 ( 1837 hom., cov: 32)

Exomes 𝑓: 0.16 ( 1687 hom. )

Consequence

CC2D1A
ENST00000586955.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.360

Publications

6 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CC2D1A	NM_017721.5 link	c.*393G>A		3_prime_UTR_variant	Exon 29 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.*393G>A		3_prime_UTR_variant	Exon 29 of 29	1	NM_017721.5	ENSP00000313601.6		Q6P1N0-1

Frequencies

GnomAD3 genomes

AF:

0.147

AC:

22352

AN:

152004

Hom.:

1836

Cov.:

show subpopulations

Gnomad AFR

AF:

0.117

Gnomad AMI

AF:

0.156

Gnomad AMR

AF:

0.130

Gnomad ASJ

AF:

0.216

Gnomad EAS

AF:

0.0848

Gnomad SAS

AF:

0.176

Gnomad FIN

AF:

0.100

Gnomad MID

AF:

0.256

Gnomad NFE

AF:

0.175

Gnomad OTH

AF:

0.167

GnomAD4 exome

AF:

0.158

AC:

18811

AN:

119196

Hom.:

1687

Cov.:

AF XY:

0.159

AC XY:

9567

AN XY:

60042

show subpopulations

African (AFR)

AF:

0.115

AC:

421

AN:

3652

American (AMR)

AF:

0.126

AC:

639

AN:

5074

Ashkenazi Jewish (ASJ)

AF:

0.216

AC:

948

AN:

4384

East Asian (EAS)

AF:

0.106

AC:

952

AN:

8986

South Asian (SAS)

AF:

0.169

AC:

1069

AN:

6344

European-Finnish (FIN)

AF:

0.0878

AC:

581

AN:

6620

Middle Eastern (MID)

AF:

0.237

AC:

142

AN:

600

European-Non Finnish (NFE)

AF:

0.168

AC:

12753

AN:

75740

Other (OTH)

AF:

0.168

AC:

1306

AN:

7796

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

765

1530

2295

3060

3825

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

204

306

408

510

<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:

0.147

AC:

22360

AN:

152122

Hom.:

1837

Cov.:

AF XY:

0.144

AC XY:

10691

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.117

AC:

4839

AN:

41510

American (AMR)

AF:

0.129

AC:

1975

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.216

AC:

750

AN:

3470

East Asian (EAS)

AF:

0.0848

AC:

437

AN:

5152

South Asian (SAS)

AF:

0.176

AC:

851

AN:

4822

European-Finnish (FIN)

AF:

0.100

AC:

1064

AN:

10598

Middle Eastern (MID)

AF:

0.262

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.175

AC:

11878

AN:

67980

Other (OTH)

AF:

0.164

AC:

347

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

962

1924

2885

3847

4809

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

250

500

750

1000

1250

<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:

0.178

Hom.:

2966

Bravo

AF:

0.149

Asia WGS

AF:

0.103

AC:

362

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

3.2

(source)

DANN

Benign

0.75

PhyloP100

0.36

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Computational scores

Splicing

Publications

Other links and lift over