19-13927978-C-T

Position:

chr19-13927978-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_017721.5(CC2D1A):c.2402C>T(p.Thr801Met) variant causes a missense change. The variant allele was found at a frequency of 0.246 in 1,613,272 control chromosomes in the GnomAD database, including 52,801 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3521 hom., cov: 29)

Exomes 𝑓: 0.25 ( 49280 hom. )

Consequence

CC2D1A
NM_017721.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 4.16

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016435385).

BP6

Variant 19-13927978-C-T is Benign according to our data. Variant chr19-13927978-C-T is described in ClinVar as [Benign]. Clinvar id is 128619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CC2D1A	NM_017721.5 link	c.2402C>T	p.Thr801Met	missense_variant	23/29	ENST00000318003.11	NP_060191.3	Q6P1N0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CC2D1A	ENST00000318003.11 link	c.2402C>T	p.Thr801Met	missense_variant	23/29	1	NM_017721.5	ENSP00000313601.6		Q6P1N0-1

Frequencies

GnomAD3 genomes

AF:

0.190

AC:

28790

AN:

151692

Hom.:

3522

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0495

Gnomad AMI

AF:

0.496

Gnomad AMR

AF:

0.169

Gnomad ASJ

AF:

0.273

Gnomad EAS

AF:

0.0694

Gnomad SAS

AF:

0.162

Gnomad FIN

AF:

0.243

Gnomad MID

AF:

0.184

Gnomad NFE

AF:

0.274

Gnomad OTH

AF:

0.191

GnomAD3 exomes

AF:

0.210

AC:

52471

AN:

249330

Hom.:

6235

AF XY:

0.216

AC XY:

29179

AN XY:

135314

show subpopulations

Gnomad AFR exome

AF:

0.0434

Gnomad AMR exome

AF:

0.156

Gnomad ASJ exome

AF:

0.260

Gnomad EAS exome

AF:

0.0690

Gnomad SAS exome

AF:

0.173

Gnomad FIN exome

AF:

0.252

Gnomad NFE exome

AF:

0.269

Gnomad OTH exome

AF:

0.234

GnomAD4 exome

AF:

0.252

AC:

368728

AN:

1461462

Hom.:

49280

Cov.:

AF XY:

0.251

AC XY:

182399

AN XY:

727034

show subpopulations

Gnomad4 AFR exome

AF:

0.0376

Gnomad4 AMR exome

AF:

0.155

Gnomad4 ASJ exome

AF:

0.258

Gnomad4 EAS exome

AF:

0.0718

Gnomad4 SAS exome

AF:

0.174

Gnomad4 FIN exome

AF:

0.260

Gnomad4 NFE exome

AF:

0.276

Gnomad4 OTH exome

AF:

0.228

GnomAD4 genome

AF:

0.190

AC:

28783

AN:

151810

Hom.:

3521

Cov.:

AF XY:

0.186

AC XY:

13830

AN XY:

74164

show subpopulations

Gnomad4 AFR

AF:

0.0493

Gnomad4 AMR

AF:

0.169

Gnomad4 ASJ

AF:

0.273

Gnomad4 EAS

AF:

0.0690

Gnomad4 SAS

AF:

0.163

Gnomad4 FIN

AF:

0.243

Gnomad4 NFE

AF:

0.274

Gnomad4 OTH

AF:

0.189

Alfa

AF:

0.249

Hom.:

10261

Bravo

AF:

0.180

TwinsUK

AF:

0.281

AC:

1041

ALSPAC

AF:

0.295

AC:

1137

ESP6500AA

AF:

0.0438

AC:

181

ESP6500EA

AF:

0.267

AC:

2245

ExAC

AF:

0.209

AC:

25349

Asia WGS

AF:

0.106

AC:

371

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not specified

Benign:1

Likely benign, no assertion criteria provided

clinical testing

Genetic Services Laboratory, University of Chicago

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 17, 2016

This alteration is classified as 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. -

Intellectual disability, autosomal recessive 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.49

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.075

T;.

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.89

D;D

MetaRNN

Benign

0.0016

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

M;M

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-2.0

N;.

REVEL

Benign

0.077

Sift

Benign

0.15

T;.

Sift4G

Benign

0.13

T;T

Polyphen

1.0

D;D

Vest4

0.19

MPC

0.77

ClinPred

0.023

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.067

gMVP

0.37

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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