2-55295654-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001365480.1(CCDC88A):c.5494C>A(p.Pro1832Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC88A NM_001365480.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.09

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC88A	NM_001365480.1	c.5494C>A	p.Pro1832Thr	missense_variant	31/33	ENST00000436346.7
CCDC88A	NM_001135597.2	c.5491C>A	p.Pro1831Thr	missense_variant	31/33
CCDC88A	NM_018084.5	c.5410C>A	p.Pro1804Thr	missense_variant	30/32
CCDC88A	NM_001254943.2	c.5269C>A	p.Pro1757Thr	missense_variant	32/34

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC88A	ENST00000436346.7	c.5494C>A	p.Pro1832Thr	missense_variant	31/33	5	NM_001365480.1	A1
	ENST00000625718.2	n.86-13178G>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 19, 2022

The c.5491C>A (p.P1831T) alteration is located in exon 31 (coding exon 31) of the CCDC88A gene. This alteration results from a C to A substitution at nucleotide position 5491, causing the proline (P) at amino acid position 1831 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.070
Cadd	Uncertain	23
Dann	Uncertain	0.98
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D;D;D;.;D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.038	D
MetaRNN	Uncertain	0.44	T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Uncertain	0.0082	D
MutationTaster	Benign	1.0	D;D;D;D;N
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-4.3	D;D;.;.;.;D;.;.;.;D;.;.;D
REVEL	Uncertain	0.32
Sift	Uncertain	0.0050	D;D;.;.;.;D;.;.;.;D;.;.;D
Sift4G	Uncertain	0.0070	D;D;.;.;.;D;.;.;.;D;.;.;T
Polyphen		1.0	D;D;D;D;.;D;.;.;.;.;.;.;.
Vest4		0.34
MutPred		0.39		.;.;.;Gain of sheet (P = 0.0028);.;Gain of sheet (P = 0.0028);.;.;.;.;.;.;.;
MVP		0.62
MPC		0.11
ClinPred		0.98	D
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.19
gMVP		0.43

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-55522790;