rs186486235

Variant names:

• chr4-15597428-C-A
• NM_001378615.1:c.4459C>A

Your query was ambiguous. Multiple possible variants found:

• chr4-15597428-C-A
• chr4-15597428-C-T

Variant summary

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

The NM_001378615.1(CC2D2A):​c.4459C>A​(p.Arg1487Ser) 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 1,400,442 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1487H) has been classified as Likely benign.

• 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: 0.748

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=0.09496519).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CC2D2A	NM_001378615.1	c.4459C>A	p.Arg1487Ser	missense_variant	Exon 35 of 37	ENST00000424120.6	NP_001365544.1
CC2D2A	NM_001080522.2	c.4459C>A	p.Arg1487Ser	missense_variant	Exon 36 of 38		NP_001073991.2
CC2D2A	NM_001378617.1	c.4312C>A	p.Arg1438Ser	missense_variant	Exon 33 of 35		NP_001365546.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CC2D2A	ENST00000424120.6	c.4459C>A	p.Arg1487Ser	missense_variant	Exon 35 of 37	5	NM_001378615.1	ENSP00000403465.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1400442 Hom.: 0 Cov.: 29 AF XY: 0.00000289 AC XY: 2 AN XY: 690934

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: 0.0000126

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.27e-7

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	0.12
BayesDel_addAF	Benign	-0.048	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	14
DANN	Benign	0.86
DEOGEN2	Benign	0.066	T;T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.50	D
LIST_S2	Uncertain	0.86	D;.
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.095	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.3	M;M
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.91	N;N
REVEL	Benign	0.061
Sift	Benign	0.74	T;T
Sift4G	Benign	0.60	T;T
Polyphen		0.39	B;B
Vest4		0.29
MutPred		0.44		Gain of glycosylation at Y1485 (P = 0.006);Gain of glycosylation at Y1485 (P = 0.006);
MVP		0.61
MPC		0.049
ClinPred		0.26	T
GERP RS		2.7
Varity_R		0.081
gMVP		0.38

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: chr4-15599051;