rs12649803

Positions:

• chr4-15575964-A-G
• chr4-15575964-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001378615.1(CC2D2A):​c.3771+1638A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 152,046 control chromosomes in the GnomAD database, including 23,532 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 0.55 (23532 hom., cov: 32)
• Consequence: CC2D2A NM_001378615.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.615

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CC2D2A	NM_001378615.1	c.3771+1638A>G		intron_variant		ENST00000424120.6	NP_001365544.1
CC2D2A	NM_001080522.2	c.3771+1638A>G		intron_variant			NP_001073991.2
CC2D2A	NM_001378617.1	c.3624+1638A>G		intron_variant			NP_001365546.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CC2D2A	ENST00000424120.6	c.3771+1638A>G		intron_variant		5	NM_001378615.1	ENSP00000403465	P1

Frequencies

GnomAD3 genomes AF: 0.554 AC: 84103 AN: 151928 Hom.: 23520 Cov.: 32

Gnomad AFR AF: 0.493

Gnomad AMI AF: 0.702

Gnomad AMR AF: 0.664

Gnomad ASJ AF: 0.580

Gnomad EAS AF: 0.512

Gnomad SAS AF: 0.575

Gnomad FIN AF: 0.518

Gnomad MID AF: 0.618

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.572

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

GnomAD4 genome AF: 0.553 AC: 84143 AN: 152046 Hom.: 23532 Cov.: 32 AF XY: 0.553 AC XY: 41103 AN XY: 74342

Gnomad4 AFR AF: 0.493

Gnomad4 AMR AF: 0.663

Gnomad4 ASJ AF: 0.580

Gnomad4 EAS AF: 0.512

Gnomad4 SAS AF: 0.575

Gnomad4 FIN AF: 0.518

Gnomad4 NFE AF: 0.569

Gnomad4 OTH AF: 0.568

Alfa AF: 0.569 Hom.: 39556

Bravo AF: 0.566

Asia WGS AF: 0.541 AC: 1881 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.18
DANN	Benign	0.21

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

Publications

LitVar

Other links and lift over

dbSNP: rs12649803; hg19: chr4-15577587;