rs758862009

Variant names:

• chr19-13909828-C-A
• rs758862009
• NM_017721.5:c.66C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-13909828-C-A
• chr19-13909828-C-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_017721.5(CC2D1A):​c.66C>A​(p.Gly22Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,435,148 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CC2D1A NM_017721.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.329

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 Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BP7: Synonymous conserved (PhyloP=0.329 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CC2D1A	NM_017721.5	c.66C>A	p.Gly22Gly	synonymous_variant	Exon 2 of 29	ENST00000318003.11	NP_060191.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CC2D1A	ENST00000318003.11	c.66C>A	p.Gly22Gly	synonymous_variant	Exon 2 of 29	1	NM_017721.5	ENSP00000313601.6
CC2D1A	ENST00000589606.5	c.66C>A	p.Gly22Gly	synonymous_variant	Exon 2 of 29	1		ENSP00000467526.1
CC2D1A	ENST00000585896.5	n.305C>A		non_coding_transcript_exon_variant	Exon 2 of 10	2
CC2D1A	ENST00000680439.1	n.224C>A		non_coding_transcript_exon_variant	Exon 2 of 7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000854 AC: 2 AN: 234144 Hom.: 0 AF XY: 0.00000787 AC XY: 1 AN XY: 127016

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000187

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1435148 Hom.: 0 Cov.: 31 AF XY: 0.00000282 AC XY: 2 AN XY: 710182

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000120

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.14e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000369 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	7.5
DANN	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs758862009; hg19: chr19-14020641;