chr2-55289187-T-G

Variant names:

• chr2-55289187-T-G
• rs2589113
• NM_001365480.1:c.*2013A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 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)

PRORSD1P (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CCDC88A	NM_001365480.1	c.*2013A>C		3_prime_UTR_variant	Exon 33 of 33	ENST00000436346.7	NP_001352409.1
CCDC88A	NM_001135597.2	c.*2013A>C		3_prime_UTR_variant	Exon 33 of 33		NP_001129069.1
CCDC88A	NM_018084.5	c.*2013A>C		3_prime_UTR_variant	Exon 32 of 32		NP_060554.3
CCDC88A	NM_001254943.2	c.*2013A>C		3_prime_UTR_variant	Exon 34 of 34		NP_001241872.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC88A	ENST00000436346.7	c.*2013A>C		3_prime_UTR_variant	Exon 33 of 33	5	NM_001365480.1	ENSP00000410608.1

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

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) AF: 0.979 AC: 417 AN: 426

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.875 AC: 7 AN: 8

Other (OTH) AF: 1.00 AC: 4 AN: 4

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

African (AFR) AF: 0.518 AC: 21491 AN: 41452

American (AMR) AF: 0.929 AC: 14204 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.941 AC: 3266 AN: 3472

East Asian (EAS) AF: 0.972 AC: 5029 AN: 5172

South Asian (SAS) AF: 0.842 AC: 4067 AN: 4828

European-Finnish (FIN) AF: 0.977 AC: 10366 AN: 10612

Middle Eastern (MID) AF: 0.888 AC: 261 AN: 294

European-Non Finnish (NFE) AF: 0.957 AC: 65091 AN: 67982

Other (OTH) AF: 0.873 AC: 1843 AN: 2110

Alfa AF: 0.915 Hom.: 235109

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
PhyloP100		1.3
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: rs2589113; hg19: chr2-55516323;