rs1059721

Positions:

• chr19-13930788-G-A
• chr19-13930788-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017721.5(CC2D1A):​c.*393G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 271,318 control chromosomes in the GnomAD database, including 3,524 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.15 (1837 hom., cov: 32)
  • Exomes 𝑓: 0.16 (1687 hom.)
• Consequence: CC2D1A NM_017721.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.360

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CC2D1A	NM_017721.5	c.*393G>A		3_prime_UTR_variant	29/29	ENST00000318003.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CC2D1A	ENST00000318003.11	c.*393G>A		3_prime_UTR_variant	29/29	1	NM_017721.5	P3

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22352 AN: 152004 Hom.: 1836 Cov.: 32

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.0848

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.167

GnomAD4 exome AF: 0.158 AC: 18811 AN: 119196 Hom.: 1687 Cov.: 0 AF XY: 0.159 AC XY: 9567 AN XY: 60042

Gnomad4 AFR exome AF: 0.115

Gnomad4 AMR exome AF: 0.126

Gnomad4 ASJ exome AF: 0.216

Gnomad4 EAS exome AF: 0.106

Gnomad4 SAS exome AF: 0.169

Gnomad4 FIN exome AF: 0.0878

Gnomad4 NFE exome AF: 0.168

Gnomad4 OTH exome AF: 0.168

GnomAD4 genome AF: 0.147 AC: 22360 AN: 152122 Hom.: 1837 Cov.: 32 AF XY: 0.144 AC XY: 10691 AN XY: 74370

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.216

Gnomad4 EAS AF: 0.0848

Gnomad4 SAS AF: 0.176

Gnomad4 FIN AF: 0.100

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.164

Alfa AF: 0.179 Hom.: 2582

Bravo AF: 0.149

Asia WGS AF: 0.103 AC: 362 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.2
DANN	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1059721; hg19: chr19-14041601; COSMIC: COSV54310042; COSMIC: COSV54310042;