rs1134634

Variant names:

• chr4-15601446-G-C
• rs1134634
• NM_001378615.1:c.*21G>C

Your query was ambiguous. Multiple possible variants found:

• chr4-15601446-G-C
• chr4-15601446-G-A
• chr4-15601446-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001378615.1(CC2D2A):​c.*21G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.584 in 1,397,134 control chromosomes in the GnomAD database, including 239,041 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.57 (24886 hom., cov: 33)
  • Exomes 𝑓: 0.58 (214155 hom.)
• Consequence: CC2D2A NM_001378615.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• 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: Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae)
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 4-15601446-G-C is Benign according to our data. Variant chr4-15601446-G-C is described in ClinVar as Benign. ClinVar VariationId is 257382.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.62 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CC2D2A	NM_001378615.1	MANE Select	c.*21G>C		3_prime_UTR	Exon 37 of 37	NP_001365544.1	Q9P2K1-4
	CC2D2A	NM_001080522.2		c.*21G>C		3_prime_UTR	Exon 38 of 38	NP_001073991.2	Q9P2K1-4
	CC2D2A	NM_001378617.1		c.*21G>C		3_prime_UTR	Exon 35 of 35	NP_001365546.1	H0Y941

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CC2D2A	ENST00000424120.6	TSL:5 MANE Select	c.*21G>C		3_prime_UTR	Exon 37 of 37	ENSP00000403465.1	Q9P2K1-4
	CC2D2A	ENST00000503292.6	TSL:1	c.*21G>C		3_prime_UTR	Exon 38 of 38	ENSP00000421809.1	Q9P2K1-4
	CC2D2A	ENST00000634028.2	TSL:1	n.*442G>C		non_coding_transcript_exon	Exon 34 of 34	ENSP00000488669.2	A0A0J9YY35

Frequencies

GnomAD3 genomes AF: 0.572 AC: 86962 AN: 151904 Hom.: 24870 Cov.: 33

Gnomad AFR AF: 0.545

Gnomad AMI AF: 0.680

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.657

Gnomad EAS AF: 0.502

Gnomad SAS AF: 0.639

Gnomad FIN AF: 0.549

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.595

Gnomad OTH AF: 0.568

GnomAD2 exomes AF: 0.579 AC: 61752 AN: 106682 AF XY: 0.584

Gnomad AFR exome AF: 0.540

Gnomad AMR exome AF: 0.516

Gnomad ASJ exome AF: 0.635

Gnomad EAS exome AF: 0.493

Gnomad FIN exome AF: 0.558

Gnomad NFE exome AF: 0.599

Gnomad OTH exome AF: 0.601

GnomAD4 exome AF: 0.585 AC: 728351 AN: 1245112 Hom.: 214155 Cov.: 21 AF XY: 0.587 AC XY: 354092 AN XY: 603104

African (AFR) AF: 0.540 AC: 15070 AN: 27926

American (AMR) AF: 0.498 AC: 9120 AN: 18316

Ashkenazi Jewish (ASJ) AF: 0.638 AC: 12048 AN: 18878

East Asian (EAS) AF: 0.527 AC: 18817 AN: 35686

South Asian (SAS) AF: 0.646 AC: 33781 AN: 52324

European-Finnish (FIN) AF: 0.554 AC: 25164 AN: 45406

Middle Eastern (MID) AF: 0.641 AC: 2544 AN: 3968

European-Non Finnish (NFE) AF: 0.587 AC: 581677 AN: 991102

Other (OTH) AF: 0.585 AC: 30130 AN: 51506

GnomAD4 genome AF: 0.572 AC: 87016 AN: 152022 Hom.: 24886 Cov.: 33 AF XY: 0.570 AC XY: 42373 AN XY: 74318

African (AFR) AF: 0.546 AC: 22627 AN: 41448

American (AMR) AF: 0.540 AC: 8244 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.657 AC: 2278 AN: 3468

East Asian (EAS) AF: 0.502 AC: 2592 AN: 5166

South Asian (SAS) AF: 0.639 AC: 3081 AN: 4824

European-Finnish (FIN) AF: 0.549 AC: 5791 AN: 10550

Middle Eastern (MID) AF: 0.613 AC: 179 AN: 292

European-Non Finnish (NFE) AF: 0.595 AC: 40414 AN: 67972

Other (OTH) AF: 0.564 AC: 1190 AN: 2110

Alfa AF: 0.494 Hom.: 1753

Bravo AF: 0.566

Asia WGS AF: 0.590 AC: 2050 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Joubert syndrome 9 (2)
-	-	2	Meckel syndrome, type 6 (2)
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.10
DANN	Benign	0.80
PhyloP100		-0.95
Mutation Taster		=100/0	polymorphism (auto)

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; COSMIC: COSV58010172; COSMIC: COSV58010172;