19-13909839-A-C

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_017721.5(CC2D1A):c.77A>C(p.Asp26Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000014 in 1,429,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CC2D1A
NM_017721.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.76

Publications

0 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: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.755

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CC2D1A	NM_017721.5 link	c.77A>C	p.Asp26Ala	missense_variant	Exon 2 of 29	ENST00000318003.11	NP_060191.3	Q6P1N0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CC2D1A	ENST00000318003.11 link	c.77A>C	p.Asp26Ala	missense_variant	Exon 2 of 29	1	NM_017721.5	ENSP00000313601.6	Q6P1N0-1
CC2D1A	ENST00000589606.5 link	c.77A>C	p.Asp26Ala	missense_variant	Exon 2 of 29	1		ENSP00000467526.1	Q6P1N0-2
CC2D1A	ENST00000585896.5 link	n.316A>C		non_coding_transcript_exon_variant	Exon 2 of 10	2
CC2D1A	ENST00000680439.1 link	n.235A>C		non_coding_transcript_exon_variant	Exon 2 of 7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000140

AC:

AN:

1429830

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

707264

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32770

American (AMR)

AF:

0.00

AC:

AN:

41898

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24416

East Asian (EAS)

AF:

0.00

AC:

AN:

38970

South Asian (SAS)

AF:

0.00

AC:

AN:

82816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52522

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5622

European-Non Finnish (NFE)

AF:

0.00000183

AC:

AN:

1091864

Other (OTH)

AF:

0.00

AC:

AN:

58952

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Apr 03, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.77A>C (p.D26A) alteration is located in exon 2 (coding exon 2) of the CC2D1A gene. This alteration results from a A to C substitution at nucleotide position 77, causing the aspartic acid (D) at amino acid position 26 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.045

BayesDel_noAF

Benign

-0.30

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.47

T;.

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.79

T;T

M_CAP

Benign

0.024

MetaRNN

Pathogenic

0.76

D;D

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.9

M;M

PhyloP100

3.8

PrimateAI

Uncertain

0.73

PROVEAN

Pathogenic

-4.5

D;.

REVEL

Benign

0.20

Sift

Uncertain

0.0050

D;.

Sift4G

Uncertain

0.011

D;D

Polyphen

0.98

D;D

Vest4

0.74

MutPred

0.47

Gain of sheet (P = 0.1451);Gain of sheet (P = 0.1451);

MVP

0.31

MPC

0.69

ClinPred

1.0

GERP RS

4.4

Varity_R

0.40

gMVP

0.80

Mutation Taster

=79/21

polymorphism

(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

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19-13909839-A-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over