2-55349333-T-C

Variant names:

• chr2-55349333-T-C
• rs10518764
• NM_001365480.1:c.882+185A>G

Variant summary

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

The NM_001365480.1(CCDC88A):​c.882+185A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0263 in 573,472 control chromosomes in the GnomAD database, including 1,391 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 0.068 (1117 hom., cov: 32)
  • Exomes 𝑓: 0.011 (274 hom.)
• Consequence: CCDC88A NM_001365480.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.67
• Publications: 4 publications found

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]

CCDC88A Gene-Disease associations (from GenCC):

• PEHO-like syndrome

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae)

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 = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC88A	NM_001365480.1	c.882+185A>G		intron_variant	Intron 9 of 32	ENST00000436346.7	NP_001352409.1
CCDC88A	NM_001135597.2	c.882+185A>G		intron_variant	Intron 9 of 32		NP_001129069.1
CCDC88A	NM_018084.5	c.882+185A>G		intron_variant	Intron 9 of 31		NP_060554.3
CCDC88A	NM_001254943.2	c.882+185A>G		intron_variant	Intron 9 of 33		NP_001241872.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC88A	ENST00000436346.7	c.882+185A>G		intron_variant	Intron 9 of 32	5	NM_001365480.1	ENSP00000410608.1

Frequencies

GnomAD3 genomes AF: 0.0673 AC: 10247 AN: 152146 Hom.: 1109 Cov.: 32

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0300

Gnomad ASJ AF: 0.0314

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.00363

Gnomad OTH AF: 0.0574

GnomAD4 exome AF: 0.0114 AC: 4805 AN: 421208 Hom.: 274 Cov.: 4 AF XY: 0.00997 AC XY: 2235 AN XY: 224282

African (AFR) AF: 0.213 AC: 2368 AN: 11106

American (AMR) AF: 0.0236 AC: 349 AN: 14796

Ashkenazi Jewish (ASJ) AF: 0.0285 AC: 368 AN: 12926

East Asian (EAS) AF: 0.00 AC: 0 AN: 28064

South Asian (SAS) AF: 0.00177 AC: 67 AN: 37954

European-Finnish (FIN) AF: 0.000240 AC: 7 AN: 29224

Middle Eastern (MID) AF: 0.0278 AC: 67 AN: 2406

European-Non Finnish (NFE) AF: 0.00373 AC: 970 AN: 260220

Other (OTH) AF: 0.0248 AC: 609 AN: 24512

GnomAD4 genome AF: 0.0676 AC: 10286 AN: 152264 Hom.: 1117 Cov.: 32 AF XY: 0.0645 AC XY: 4805 AN XY: 74444

African (AFR) AF: 0.225 AC: 9322 AN: 41514

American (AMR) AF: 0.0300 AC: 459 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0314 AC: 109 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4828

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10620

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.00363 AC: 247 AN: 68016

Other (OTH) AF: 0.0568 AC: 120 AN: 2114

Alfa AF: 0.0283 Hom.: 115

Bravo AF: 0.0762

Asia WGS AF: 0.0210 AC: 73 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.028
DANN	Benign	0.38
PhyloP100		-4.7
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: rs10518764; hg19: chr2-55576469;