Genetic Variant CC2D1A:p.Arg19Ser (chr19-13906496-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_017721.5(CC2D1A):c.55C>A(p.Arg19Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000149 in 1,340,140 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R19C) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

CC2D1A
NM_017721.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.01

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 links:

BRME1 (HGNC:28153): (break repair meiotic recombinase recruitment factor 1) Predicted to be involved in meiosis I and spermatogenesis. Predicted to be located in chromosome. [provided by Alliance of Genome Resources, Apr 2022]

BRME1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3022155).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CC2D1A	NM_017721.5 link	c.55C>A	p.Arg19Ser	missense_variant	Exon 1 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.55C>A	p.Arg19Ser	missense_variant	Exon 1 of 29	1	NM_017721.5	ENSP00000313601.6		Q6P1N0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000149

AC:

AN:

1340140

Hom.:

Cov.:

AF XY:

0.00000151

AC XY:

AN XY:

660436

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27656

American (AMR)

AF:

0.00

AC:

AN:

29180

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23718

East Asian (EAS)

AF:

0.00

AC:

AN:

29634

South Asian (SAS)

AF:

0.0000268

AC:

AN:

74616

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37910

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4904

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1056824

Other (OTH)

AF:

0.00

AC:

AN:

55698

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.78

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.39

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.041

T;.

Eigen

Benign

0.16

Eigen_PC

Benign

0.15

FATHMM_MKL

Benign

0.38

LIST_S2

Uncertain

0.89

D;D

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.30

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.97

L;L

PhyloP100

1.0

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-1.5

N;.

REVEL

Benign

0.16

Sift

Benign

0.078

T;.

Sift4G

Uncertain

0.0050

D;D

Polyphen

0.99

D;D

Vest4

0.29

MutPred

0.36

Loss of methylation at R19 (P = 0.0355);Loss of methylation at R19 (P = 0.0355);

MVP

0.50

MPC

0.60

ClinPred

0.87

GERP RS

2.9

PromoterAI

0.034

Neutral

(source)

Varity_R

0.20

gMVP

0.51

Mutation Taster

=88/12

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over