NM_001378615.1:c.3652C>G

Variant names:

• chr4-15574207-C-G
• NM_001378615.1:c.3652C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001378615.1(CC2D2A):​c.3652C>G​(p.Arg1218Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,398,998 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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: CC2D2A NM_001378615.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10886347).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CC2D2A	NM_001378615.1	c.3652C>G	p.Arg1218Gly	missense_variant	Exon 29 of 37	ENST00000424120.6	NP_001365544.1
CC2D2A	NM_001080522.2	c.3652C>G	p.Arg1218Gly	missense_variant	Exon 30 of 38		NP_001073991.2
CC2D2A	NM_001378617.1	c.3505C>G	p.Arg1169Gly	missense_variant	Exon 27 of 35		NP_001365546.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CC2D2A	ENST00000424120.6	c.3652C>G	p.Arg1218Gly	missense_variant	Exon 29 of 37	5	NM_001378615.1	ENSP00000403465.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1398998 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 689998

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: 0.00000185

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	Benign	0.093
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.13	T;T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.57
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.88	D;.
M_CAP	Benign	0.062	D
MetaRNN	Benign	0.11	T;T
MetaSVM	Uncertain	-0.028	T
MutationAssessor	Benign	1.2	L;L
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.9	N;N
REVEL	Uncertain	0.36
Sift	Benign	0.28	T;T
Sift4G	Benign	0.21	T;T
Polyphen		0.0040	B;B
Vest4		0.25
MutPred		0.50		Gain of sheet (P = 0.0043);Gain of sheet (P = 0.0043);
MVP		0.72
MPC		0.051
ClinPred		0.17	T
GERP RS		0.72
Varity_R		0.16
gMVP		0.33

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: chr4-15575830;