2-55289187-T-G

Variant summary

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

The NM_001365480.1(CCDC88A):c.*2013A>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 0.832 in 152,558 control chromosomes in the GnomAD database, including 55,696 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 0.83 (55486 hom., cov: 31)
  • Exomes 𝑓: 0.98 (210 hom.)
• Consequence: CCDC88A NM_001365480.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28

Genes affected

CCDC88A (HGNC:25523): (coiled-coil domain containing 88A) This gene encodes a member of the Girdin family of coiled-coil domain containing proteins. The encoded protein is an actin-binding protein that is activated by the serine/threonine kinase Akt and plays a role in cytoskeleton remodeling and cell migration. The encoded protein also enhances Akt signaling by mediating phosphoinositide 3-kinase (PI3K)-dependent activation of Akt by growth factor receptor tyrosine kinases and G protein-coupled receptors. Increased expression of this gene and phosphorylation of the encoded protein may play a role in cancer metastasis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.951 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC88A	NM_001365480.1	c.*2013A>C		3_prime_UTR_variant	33/33	ENST00000436346.7
CCDC88A	NM_001135597.2	c.*2013A>C		3_prime_UTR_variant	33/33
CCDC88A	NM_001254943.2	c.*2013A>C		3_prime_UTR_variant	34/34
CCDC88A	NM_018084.5	c.*2013A>C		3_prime_UTR_variant	32/32

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC88A	ENST00000436346.7	c.*2013A>C		3_prime_UTR_variant	33/33	5	NM_001365480.1	A1
	ENST00000625718.2	n.85+6753T>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.832 AC: 126435 AN: 152002 Hom.: 55471 Cov.: 31

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.955

Gnomad AMR AF: 0.929

Gnomad ASJ AF: 0.941

Gnomad EAS AF: 0.972

Gnomad SAS AF: 0.842

Gnomad FIN AF: 0.977

Gnomad MID AF: 0.896

Gnomad NFE AF: 0.957

Gnomad OTH AF: 0.872

GnomAD4 exome AF: 0.977 AC: 428 AN: 438 Hom.: 210 Cov.: 0 AF XY: 0.981 AC XY: 259 AN XY: 264

Gnomad4 FIN exome AF: 0.979

Gnomad4 NFE exome AF: 0.875

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.832 AC: 126489 AN: 152120 Hom.: 55486 Cov.: 31 AF XY: 0.836 AC XY: 62131 AN XY: 74362

Gnomad4 AFR AF: 0.518

Gnomad4 AMR AF: 0.929

Gnomad4 ASJ AF: 0.941

Gnomad4 EAS AF: 0.972

Gnomad4 SAS AF: 0.842

Gnomad4 FIN AF: 0.977

Gnomad4 NFE AF: 0.957

Gnomad4 OTH AF: 0.873

Alfa AF: 0.936 Hom.: 114364

Bravo AF: 0.818

Asia WGS AF: 0.886 AC: 3082 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	8.9
Dann	Benign	0.60

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: rs2589113; hg19: chr2-55516323;