rs1059721

Variant names:

• chr19-13930788-G-A
• rs1059721
• NM_017721.5:c.*393G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• intellectual disability, autosomal recessive 3

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017721.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CC2D1A	NM_017721.5	MANE Select	c.*393G>A		3_prime_UTR	Exon 29 of 29	NP_060191.3
	CC2D1A	NM_001411138.1		c.*393G>A		3_prime_UTR	Exon 29 of 29	NP_001398067.1	Q6P1N0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CC2D1A	ENST00000318003.11	TSL:1 MANE Select	c.*393G>A		3_prime_UTR	Exon 29 of 29	ENSP00000313601.6	Q6P1N0-1
	CC2D1A	ENST00000586955.5	TSL:1	n.*1516G>A		non_coding_transcript_exon	Exon 24 of 24	ENSP00000465376.1	K7EJY5
	CC2D1A	ENST00000586955.5	TSL:1	n.*1516G>A		3_prime_UTR	Exon 24 of 24	ENSP00000465376.1	K7EJY5

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

African (AFR) AF: 0.115 AC: 421 AN: 3652

American (AMR) AF: 0.126 AC: 639 AN: 5074

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 948 AN: 4384

East Asian (EAS) AF: 0.106 AC: 952 AN: 8986

South Asian (SAS) AF: 0.169 AC: 1069 AN: 6344

European-Finnish (FIN) AF: 0.0878 AC: 581 AN: 6620

Middle Eastern (MID) AF: 0.237 AC: 142 AN: 600

European-Non Finnish (NFE) AF: 0.168 AC: 12753 AN: 75740

Other (OTH) AF: 0.168 AC: 1306 AN: 7796

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

African (AFR) AF: 0.117 AC: 4839 AN: 41510

American (AMR) AF: 0.129 AC: 1975 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 750 AN: 3470

East Asian (EAS) AF: 0.0848 AC: 437 AN: 5152

South Asian (SAS) AF: 0.176 AC: 851 AN: 4822

European-Finnish (FIN) AF: 0.100 AC: 1064 AN: 10598

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.175 AC: 11878 AN: 67980

Other (OTH) AF: 0.164 AC: 347 AN: 2112

Alfa AF: 0.178 Hom.: 2966

Bravo AF: 0.149

Asia WGS AF: 0.103 AC: 362 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.2
DANN	Benign	0.75
PhyloP100		0.36
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1059721;

hg19: chr19-14041601;

COSMIC: COSV54310042;

COSMIC: COSV54310042;