Variant 19-13919876-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_017721.5(CC2D1A):c.1281T>C(p.Gly427=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 1,611,382 control chromosomes in the GnomAD database, including 60,576 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 14790 hom., cov: 30)

Exomes 𝑓: 0.23 ( 45786 hom. )

Consequence

CC2D1A
NM_017721.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -3.31

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 19-13919876-T-C is Benign according to our data. Variant chr19-13919876-T-C is described in ClinVar as [Benign]. Clinvar id is 128615.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.31 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CC2D1A	NM_017721.5 linkuse as main transcript	c.1281T>C	p.Gly427=	synonymous_variant	12/29	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.1281T>C	p.Gly427=	synonymous_variant	12/29	1	NM_017721.5	ENSP00000313601	P3	Q6P1N0-1

Frequencies

GnomAD3 genomes

AF:

0.371

AC:

56173

AN:

151536

Hom.:

14735

Cov.:

show subpopulations

Gnomad AFR

AF:

0.745

Gnomad AMI

AF:

0.0890

Gnomad AMR

AF:

0.361

Gnomad ASJ

AF:

0.171

Gnomad EAS

AF:

0.309

Gnomad SAS

AF:

0.288

Gnomad FIN

AF:

0.153

Gnomad MID

AF:

0.168

Gnomad NFE

AF:

0.206

Gnomad OTH

AF:

0.322

GnomAD3 exomes

AF:

0.274

AC:

68267

AN:

249124

Hom.:

11953

AF XY:

0.261

AC XY:

35332

AN XY:

135224

show subpopulations

Gnomad AFR exome

AF:

0.756

Gnomad AMR exome

AF:

0.367

Gnomad ASJ exome

AF:

0.181

Gnomad EAS exome

AF:

0.299

Gnomad SAS exome

AF:

0.268

Gnomad FIN exome

AF:

0.168

Gnomad NFE exome

AF:

0.207

Gnomad OTH exome

AF:

0.256

GnomAD4 exome

AF:

0.231

AC:

337799

AN:

1459732

Hom.:

45786

Cov.:

AF XY:

0.230

AC XY:

167054

AN XY:

726136

show subpopulations

Gnomad4 AFR exome

AF:

0.768

Gnomad4 AMR exome

AF:

0.367

Gnomad4 ASJ exome

AF:

0.183

Gnomad4 EAS exome

AF:

0.280

Gnomad4 SAS exome

AF:

0.263

Gnomad4 FIN exome

AF:

0.173

Gnomad4 NFE exome

AF:

0.208

Gnomad4 OTH exome

AF:

0.253

GnomAD4 genome

AF:

0.371

AC:

56292

AN:

151650

Hom.:

14790

Cov.:

AF XY:

0.367

AC XY:

27182

AN XY:

74118

show subpopulations

Gnomad4 AFR

AF:

0.746

Gnomad4 AMR

AF:

0.361

Gnomad4 ASJ

AF:

0.171

Gnomad4 EAS

AF:

0.309

Gnomad4 SAS

AF:

0.287

Gnomad4 FIN

AF:

0.153

Gnomad4 NFE

AF:

0.206

Gnomad4 OTH

AF:

0.327

Alfa

AF:

0.281

Hom.:

3679

Bravo

AF:

0.403

Asia WGS

AF:

0.372

AC:

1290

AN:

3478

EpiCase

AF:

0.205

EpiControl

AF:

0.202

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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

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 11, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.59

DANN

Benign

0.47

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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