19-13918535-G-A

Position:

chr19-13918535-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_017721.5(CC2D1A):c.905G>A(p.Arg302Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00046 in 1,613,760 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0026 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00023 ( 1 hom. )

Consequence

CC2D1A
NM_017721.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 2.11

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010322213).

BP6

Variant 19-13918535-G-A is Benign according to our data. Variant chr19-13918535-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 376960.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CC2D1A	NM_017721.5 linkuse as main transcript	c.905G>A	p.Arg302Gln	missense_variant	8/29	ENST00000318003.11	NP_060191.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CC2D1A	ENST00000318003.11 linkuse as main transcript	c.905G>A	p.Arg302Gln	missense_variant	8/29	1	NM_017721.5	ENSP00000313601	P3	Q6P1N0-1

Frequencies

GnomAD3 genomes

AF:

0.00264

AC:

402

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00925

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000671

AC:

167

AN:

248870

Hom.:

AF XY:

0.000563

AC XY:

AN XY:

135066

show subpopulations

Gnomad AFR exome

AF:

0.00886

Gnomad AMR exome

AF:

0.000667

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000443

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000233

AC:

341

AN:

1461504

Hom.:

Cov.:

AF XY:

0.000209

AC XY:

152

AN XY:

727086

show subpopulations

Gnomad4 AFR exome

AF:

0.00765

Gnomad4 AMR exome

AF:

0.000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000234

Gnomad4 OTH exome

AF:

0.000447

GnomAD4 genome

AF:

0.00263

AC:

401

AN:

152256

Hom.:

Cov.:

AF XY:

0.00249

AC XY:

185

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.00920

Gnomad4 AMR

AF:

0.000850

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000394

Hom.:

Bravo

AF:

0.00264

ESP6500AA

AF:

0.00784

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000819

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Dec 06, 2016	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2023	CC2D1A: BP4 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 12, 2021

This alteration is classified as likely 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. -

CC2D1A-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 21, 2023

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.044

T;.

Eigen

Benign

0.11

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.84

T;T

MetaRNN

Benign

0.010

T;T

MetaSVM

Benign

-0.47

MutationAssessor

Benign

1.9

L;L

MutationTaster

Benign

0.53

D;D

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.1

N;.

REVEL

Benign

0.19

Sift

Benign

0.063

T;.

Sift4G

Benign

0.13

T;T

Polyphen

0.99

D;P

Vest4

0.38

MVP

0.80

MPC

0.25

ClinPred

0.0057

GERP RS

2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.065

gMVP

0.18

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over