2-130339209-C-T

Position:

• chr2-130339209-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The ENST00000259229.7(CCDC115):​c.454G>A​(p.Ala152Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CCDC115 ENST00000259229.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.14

Genes affected

CCDC115 (HGNC:28178): (coiled-coil domain containing 115) The protein encoded by this gene has been observed to localize to the endoplasmic reticulum (ER)-Golgi intermediate compartment (ERGIC) and coat protein complex I (COPI) vesicles in some human cells. The encoded protein shares some homology with the yeast V-ATPase assembly factor Vma22p, and the orthologous protein in mouse promotes cell proliferation and suppresses cell death. Defects in this gene are a cause of congenital disorder of glycosylation, type IIo in humans. [provided by RefSeq, Mar 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.832

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC115	NM_032357.4	c.454G>A	p.Ala152Thr	missense_variant	5/5	ENST00000259229.7	NP_115733.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC115	ENST00000259229.7	c.454G>A	p.Ala152Thr	missense_variant	5/5	1	NM_032357.4	ENSP00000259229	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 07, 2022

The c.454G>A (p.A152T) alteration is located in exon 5 (coding exon 5) of the CCDC115 gene. This alteration results from a G to A substitution at nucleotide position 454, causing the alanine (A) at amino acid position 152 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	0.32
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.30	T;T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.82	T;T
M_CAP	Pathogenic	0.44	D
MetaRNN	Pathogenic	0.83	D;D
MetaSVM	Pathogenic	0.95	D
MutationAssessor	Pathogenic	3.2	M;.
MutationTaster	Benign	0.90	D;D;D
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-3.3	D;D
REVEL	Pathogenic	0.77
Sift	Uncertain	0.0070	D;D
Sift4G	Benign	0.071	T;D
Polyphen		1.0	D;D
Vest4		0.65
MutPred		0.56		Gain of relative solvent accessibility (P = 0.0479);.;
MVP		0.98
MPC		0.89
ClinPred		0.99	D
GERP RS		4.0
Varity_R		0.44
gMVP		0.69

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: chr2-131096782;