rs200121704

Positions:

chr19-13918779-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_017721.5(CC2D1A):c.980C>T(p.Ser327Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00864 in 1,613,338 control chromosomes in the GnomAD database, including 105 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 0.0069 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0088 ( 101 hom. )

Consequence

CC2D1A
NM_017721.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.177

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=0.004861355).

BP6

Variant 19-13918779-C-T is Benign according to our data. Variant chr19-13918779-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 128624.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0069 (1051/152260) while in subpopulation SAS AF= 0.0139 (67/4826). AF 95% confidence interval is 0.0112. There are 4 homozygotes in gnomad4. There are 530 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CC2D1A	NM_017721.5 linkuse as main transcript	c.980C>T	p.Ser327Leu	missense_variant	9/29	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.980C>T	p.Ser327Leu	missense_variant	9/29	1	NM_017721.5	ENSP00000313601	P3	Q6P1N0-1

Frequencies

GnomAD3 genomes

AF:

0.00691

AC:

1051

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00157

Gnomad AMI

AF:

0.0175

Gnomad AMR

AF:

0.0104

Gnomad ASJ

AF:

0.0196

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0135

Gnomad FIN

AF:

0.00188

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00929

Gnomad OTH

AF:

0.00860

GnomAD3 exomes

AF:

0.00920

AC:

2275

AN:

247258

Hom.:

AF XY:

0.0101

AC XY:

1351

AN XY:

134364

show subpopulations

Gnomad AFR exome

AF:

0.00112

Gnomad AMR exome

AF:

0.00732

Gnomad ASJ exome

AF:

0.0222

Gnomad EAS exome

AF:

0.000334

Gnomad SAS exome

AF:

0.0167

Gnomad FIN exome

AF:

0.00228

Gnomad NFE exome

AF:

0.0104

Gnomad OTH exome

AF:

0.0103

GnomAD4 exome

AF:

0.00883

AC:

12895

AN:

1461078

Hom.:

101

Cov.:

AF XY:

0.00926

AC XY:

6732

AN XY:

726804

show subpopulations

Gnomad4 AFR exome

AF:

0.00114

Gnomad4 AMR exome

AF:

0.00739

Gnomad4 ASJ exome

AF:

0.0222

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0173

Gnomad4 FIN exome

AF:

0.00222

Gnomad4 NFE exome

AF:

0.00871

Gnomad4 OTH exome

AF:

0.00909

GnomAD4 genome

AF:

0.00690

AC:

1051

AN:

152260

Hom.:

Cov.:

AF XY:

0.00712

AC XY:

530

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.00156

Gnomad4 AMR

AF:

0.0104

Gnomad4 ASJ

AF:

0.0196

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0139

Gnomad4 FIN

AF:

0.00188

Gnomad4 NFE

AF:

0.00929

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.00960

Hom.:

Bravo

AF:

0.00670

TwinsUK

AF:

0.00674

AC:

ALSPAC

AF:

0.0106

AC:

ESP6500AA

AF:

0.000498

AC:

ESP6500EA

AF:

0.00793

AC:

ExAC

AF:

0.00928

AC:

1122

Asia WGS

AF:

0.00751

AC:

AN:

3476

EpiCase

AF:

0.0104

EpiControl

AF:

0.0132

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Nov 15, 2016	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Nov 17, 2015

- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 24, 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. -

CC2D1A-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 21, 2019

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). -

Intellectual disability, autosomal recessive 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Jul 08, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.70

CADD

Benign

7.0

DANN

Benign

0.86

DEOGEN2

Benign

0.040

T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.28

T;T

MetaRNN

Benign

0.0049

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.4

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.62

N;.

REVEL

Benign

0.052

Sift

Benign

0.33

T;.

Sift4G

Benign

0.63

T;T

Polyphen

0.0

B;B

Vest4

0.072

MVP

0.20

MPC

0.19

ClinPred

0.0041

GERP RS

1.5

Varity_R

0.025

gMVP

0.12

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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