4-15599584-C-G

Variant names:

• chr4-15599584-C-G
• NM_001378615.1:c.4552C>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001378615.1(CC2D2A):​c.4552C>G​(p.Arg1518Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,454,704 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CC2D2A NM_001378615.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.89

Genes affected

CC2D2A (HGNC:29253): (coiled-coil and C2 domain containing 2A) This gene encodes a coiled-coil and calcium binding domain protein that appears to play a critical role in cilia formation. Mutations in this gene cause Meckel syndrome type 6, as well as Joubert syndrome type 9. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.889

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CC2D2A	NM_001378615.1	c.4552C>G	p.Arg1518Gly	missense_variant	Exon 36 of 37	ENST00000424120.6	NP_001365544.1
CC2D2A	NM_001080522.2	c.4552C>G	p.Arg1518Gly	missense_variant	Exon 37 of 38		NP_001073991.2
CC2D2A	NM_001378617.1	c.4405C>G	p.Arg1469Gly	missense_variant	Exon 34 of 35		NP_001365546.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CC2D2A	ENST00000424120.6	c.4552C>G	p.Arg1518Gly	missense_variant	Exon 36 of 37	5	NM_001378615.1	ENSP00000403465.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1454704 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 722894

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: 0.00000181

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.74	D;D
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.97	D;.
M_CAP	Uncertain	0.18	D
MetaRNN	Pathogenic	0.89	D;D
MetaSVM	Uncertain	-0.11	T
MutationAssessor	Uncertain	2.8	M;M
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-4.7	D;D
REVEL	Uncertain	0.62
Sift	Uncertain	0.0040	D;D
Sift4G	Uncertain	0.0090	D;D
Polyphen		0.99	D;D
Vest4		0.91
MutPred		0.49		Loss of helix (P = 0.0041);Loss of helix (P = 0.0041);
MVP		0.82
MPC		0.24
ClinPred		0.99	D
GERP RS		3.0
Varity_R		0.57
gMVP		0.72

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: chr4-15601207;