4-15480352-A-G

Variant names:

• chr4-15480352-A-G
• rs1861048
• NM_001378615.1:c.124-352A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080522.2(CC2D2A):​c.124-352A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 152,046 control chromosomes in the GnomAD database, including 21,171 homozygotes. 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: 𝑓 0.52 (21171 hom., cov: 32)
• Consequence: CC2D2A NM_001080522.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.184
• Publications: 5 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080522.2. 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.124-352A>G		intron	N/A	NP_001365544.1
	CC2D2A	NM_001080522.2		c.124-352A>G		intron	N/A	NP_001073991.2
	CC2D2A	NM_001378617.1		c.-24-352A>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.124-352A>G		intron	N/A	ENSP00000403465.1
	CC2D2A	ENST00000503292.6	TSL:1	c.124-352A>G		intron	N/A	ENSP00000421809.1
	CC2D2A	ENST00000503658.2	TSL:1	c.230-352A>G		intron	N/A	ENSP00000426846.1

Frequencies

GnomAD3 genomes AF: 0.519 AC: 78794 AN: 151928 Hom.: 21138 Cov.: 32

Gnomad AFR AF: 0.655

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.415

Gnomad FIN AF: 0.446

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.512

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.519 AC: 78875 AN: 152046 Hom.: 21171 Cov.: 32 AF XY: 0.517 AC XY: 38405 AN XY: 74324

African (AFR) AF: 0.655 AC: 27163 AN: 41460

American (AMR) AF: 0.534 AC: 8166 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.410 AC: 1423 AN: 3470

East Asian (EAS) AF: 0.554 AC: 2866 AN: 5172

South Asian (SAS) AF: 0.414 AC: 1991 AN: 4812

European-Finnish (FIN) AF: 0.446 AC: 4713 AN: 10566

Middle Eastern (MID) AF: 0.479 AC: 140 AN: 292

European-Non Finnish (NFE) AF: 0.456 AC: 30979 AN: 67976

Other (OTH) AF: 0.517 AC: 1088 AN: 2106

Alfa AF: 0.477 Hom.: 21742

Bravo AF: 0.532

Asia WGS AF: 0.504 AC: 1755 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.7
DANN	Benign	0.84
PhyloP100		-0.18
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: rs1861048; hg19: chr4-15481976;