ENST00000634028.2:n.*442G>T

Variant names:

• chr4-15601446-G-T
• rs1134634
• ENST00000634028.2:n.*442G>T

Variant summary

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

The ENST00000634028.2(CC2D2A):​n.*442G>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000024 in 1,248,372 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)
  • Exomes 𝑓: 0.0000024 (0 hom.)
• Consequence: CC2D2A ENST00000634028.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.946
• Publications: 32 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=-0.62).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000634028.2. 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.*21G>T		3_prime_UTR	Exon 37 of 37	NP_001365544.1
	CC2D2A	NM_001080522.2		c.*21G>T		3_prime_UTR	Exon 38 of 38	NP_001073991.2
	CC2D2A	NM_001378617.1		c.*21G>T		3_prime_UTR	Exon 35 of 35	NP_001365546.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CC2D2A	ENST00000634028.2	TSL:1	n.*442G>T		non_coding_transcript_exon	Exon 34 of 34	ENSP00000488669.2
	CC2D2A	ENST00000424120.6	TSL:5 MANE Select	c.*21G>T		3_prime_UTR	Exon 37 of 37	ENSP00000403465.1
	CC2D2A	ENST00000503292.6	TSL:1	c.*21G>T		3_prime_UTR	Exon 38 of 38	ENSP00000421809.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000937 AC: 1 AN: 106682 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000377

GnomAD4 exome AF: 0.00000240 AC: 3 AN: 1248372 Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0 AN XY: 604696

African (AFR) AF: 0.00 AC: 0 AN: 27990

American (AMR) AF: 0.00 AC: 0 AN: 18372

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18902

East Asian (EAS) AF: 0.00 AC: 0 AN: 35754

South Asian (SAS) AF: 0.00 AC: 0 AN: 52504

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45458

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3974

European-Non Finnish (NFE) AF: 0.00000101 AC: 1 AN: 993802

Other (OTH) AF: 0.0000387 AC: 2 AN: 51616

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 1753

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	0.11
DANN	Benign	0.79
PhyloP100		-0.95

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

Other links and lift over

dbSNP: rs1134634; hg19: chr4-15603069;