rs11728800

Variant names:

• chr4-15473372-C-T
• rs11728800
• NM_001378615.1:c.-18-2543C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-15473372-C-T
• chr4-15473372-C-A
• chr4-15473372-C-G

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.-18-2543C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 151,962 control chromosomes in the GnomAD database, including 6,692 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (6692 hom., cov: 31)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: CC2D2A NM_001378615.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.196
• Publications: 6 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=-0.91).
• BP6: Variant 4-15473372-C-T is Benign according to our data. Variant chr4-15473372-C-T is described in ClinVar as Benign. ClinVar VariationId is 1178118.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.375 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.-18-2543C>T		intron	N/A	NP_001365544.1	Q9P2K1-4
	CC2D2A	NM_001080522.2		c.-19+117C>T		intron	N/A	NP_001073991.2	Q9P2K1-4
	CC2D2A	NM_020785.2		c.-19+117C>T		intron	N/A	NP_065836.2	Q9P2K1-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CC2D2A	ENST00000424120.6	TSL:5 MANE Select	c.-18-2543C>T		intron	N/A	ENSP00000403465.1	Q9P2K1-4
	CC2D2A	ENST00000503292.6	TSL:1	c.-19+117C>T		intron	N/A	ENSP00000421809.1	Q9P2K1-4
	CC2D2A	ENST00000503658.2	TSL:1	c.-19+117C>T		intron	N/A	ENSP00000426846.1	Q9P2K1-5

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40081 AN: 151840 Hom.: 6681 Cov.: 31

Gnomad AFR AF: 0.0697

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.314

Gnomad EAS AF: 0.0751

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.277

GnomAD4 exome AF: 0.500 AC: 2 AN: 4 Hom.: 0 AF XY: 0.500 AC XY: 2 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 2 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.264 AC: 40108 AN: 151958 Hom.: 6692 Cov.: 31 AF XY: 0.261 AC XY: 19407 AN XY: 74244

African (AFR) AF: 0.0695 AC: 2885 AN: 41496

American (AMR) AF: 0.268 AC: 4083 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.314 AC: 1088 AN: 3468

East Asian (EAS) AF: 0.0754 AC: 390 AN: 5170

South Asian (SAS) AF: 0.282 AC: 1358 AN: 4810

European-Finnish (FIN) AF: 0.343 AC: 3603 AN: 10506

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.378 AC: 25713 AN: 67944

Other (OTH) AF: 0.282 AC: 596 AN: 2110

Alfa AF: 0.342 Hom.: 16399

Bravo AF: 0.248

Asia WGS AF: 0.156 AC: 547 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.57
PhyloP100		-0.20
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: rs11728800; hg19: chr4-15474996;