chr4-15586274-A-G

Variant names:

• chr4-15586274-A-G
• rs6832789
• NM_001378615.1:c.4065+28A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001378615.1(CC2D2A):​c.4065+28A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CC2D2A NM_001378615.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.206
• Publications: 9 publications found

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]

CC2D2A Gene-Disease associations (from GenCC):

• ciliopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Joubert syndrome 9

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P
• retinitis pigmentosa 93

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• COACH syndrome 1

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Joubert syndrome with oculorenal defect

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Meckel syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378615.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CC2D2A	NM_001378615.1	MANE Select	c.4065+28A>G		intron	N/A	NP_001365544.1
	CC2D2A	NM_001080522.2		c.4065+28A>G		intron	N/A	NP_001073991.2
	CC2D2A	NM_001378617.1		c.3918+28A>G		intron	N/A	NP_001365546.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CC2D2A	ENST00000424120.6	TSL:5 MANE Select	c.4065+28A>G		intron	N/A	ENSP00000403465.1
	CC2D2A	ENST00000503292.6	TSL:1	c.4065+28A>G		intron	N/A	ENSP00000421809.1
	CC2D2A	ENST00000634028.2	TSL:1	n.3918+28A>G		intron	N/A	ENSP00000488669.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1242790 Hom.: 0 Cov.: 16 AF XY: 0.00 AC XY: 0 AN XY: 619064

African (AFR) AF: 0.00 AC: 0 AN: 28028

American (AMR) AF: 0.00 AC: 0 AN: 33600

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22542

East Asian (EAS) AF: 0.00 AC: 0 AN: 35756

South Asian (SAS) AF: 0.00 AC: 0 AN: 63096

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50230

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5182

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 952506

Other (OTH) AF: 0.00 AC: 0 AN: 51850

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.74
DANN	Benign	0.81
PhyloP100		0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6832789; hg19: chr4-15587897;