NM_001365480.1:c.2315delT

Variant names:

• chr2-55334505-TA-T
• rs879255649
• NM_001365480.1:c.2315delT

Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_001365480.1(CCDC88A):​c.2315delT​(p.Leu772fs) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC88A NM_001365480.1 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 8.95
• Publications: 0 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: Pathogenic. The variant received 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 2-55334505-TA-T is Pathogenic according to our data. Variant chr2-55334505-TA-T is described in ClinVar as Pathogenic. ClinVar VariationId is 253149.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365480.1. 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
	CCDC88A	NM_001365480.1	MANE Select	c.2315delT	p.Leu772fs	frameshift	Exon 15 of 33	NP_001352409.1
	CCDC88A	NM_001135597.2		c.2315delT	p.Leu772fs	frameshift	Exon 15 of 33	NP_001129069.1
	CCDC88A	NM_018084.5		c.2315delT	p.Leu772fs	frameshift	Exon 15 of 32	NP_060554.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC88A	ENST00000436346.7	TSL:5 MANE Select	c.2315delT	p.Leu772fs	frameshift	Exon 15 of 33	ENSP00000410608.1
	CCDC88A	ENST00000336838.10	TSL:1	c.2315delT	p.Leu772fs	frameshift	Exon 15 of 33	ENSP00000338728.6
	CCDC88A	ENST00000263630.13	TSL:1	c.2315delT	p.Leu772fs	frameshift	Exon 15 of 32	ENSP00000263630.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

PEHO-like syndrome Pathogenic:1

Nov 12, 2024

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.9
Mutation Taster		=0/200	disease causing (ClinVar)

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: rs879255649; hg19: chr2-55561641;