rs10410239

Variant names:

• chr19-13919876-T-C
• rs10410239
• NM_017721.5:c.1281T>C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_017721.5(CC2D1A):​c.1281T>C​(p.Gly427Gly) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -3.31

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]

ACMG classification

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 rank	MANE	Protein	UniProt
CC2D1A	NM_017721.5	c.1281T>C	p.Gly427Gly	synonymous_variant	Exon 12 of 29	ENST00000318003.11	NP_060191.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CC2D1A	ENST00000318003.11	c.1281T>C	p.Gly427Gly	synonymous_variant	Exon 12 of 29	1	NM_017721.5	ENSP00000313601.6

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56173 AN: 151536 Hom.: 14735 Cov.: 30

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

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.: 33 AF XY: 0.230 AC XY: 167054 AN XY: 726136

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.: 30 AF XY: 0.367 AC XY: 27182 AN XY: 74118

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

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

-

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

Mar 11, 2016

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Other links and lift over

dbSNP: rs10410239; hg19: chr19-14030689; COSMIC: COSV58784792; COSMIC: COSV58784792;