19-13909827-G-T

Variant names:

• chr19-13909827-G-T
• NM_017721.5:c.65G>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_017721.5(CC2D1A):​c.65G>T​(p.Gly22Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CC2D1A NM_017721.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.85

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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.837

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CC2D1A	NM_017721.5	c.65G>T	p.Gly22Val	missense_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.65G>T	p.Gly22Val	missense_variant	Exon 2 of 29	1	NM_017721.5	ENSP00000313601.6
CC2D1A	ENST00000589606.5	c.65G>T	p.Gly22Val	missense_variant	Exon 2 of 29	1		ENSP00000467526.1
CC2D1A	ENST00000585896.5	n.304G>T		non_coding_transcript_exon_variant	Exon 2 of 10	2
CC2D1A	ENST00000680439.1	n.223G>T		non_coding_transcript_exon_variant	Exon 2 of 7

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1435956 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 710610

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.57	D;.
Eigen	Pathogenic	0.84
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D;D
M_CAP	Benign	0.057	D
MetaRNN	Pathogenic	0.84	D;D
MetaSVM	Benign	-0.75	T
MutationAssessor	Pathogenic	3.1	M;M
PrimateAI	Pathogenic	0.84	D
PROVEAN	Pathogenic	-6.4	D;.
REVEL	Uncertain	0.43
Sift	Uncertain	0.0010	D;.
Sift4G	Uncertain	0.0040	D;D
Polyphen		0.99	D;D
Vest4		0.82
MutPred		0.62		Loss of disorder (P = 0.0405);Loss of disorder (P = 0.0405);
MVP		0.61
MPC		0.91
ClinPred		1.0	D
GERP RS		5.4
Varity_R		0.88
gMVP		0.94

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-14020640;