2-130340975-G-T

Variant names:

• chr2-130340975-G-T
• rs771683316
• NM_032357.4:c.363C>A

Variant summary

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

The NM_032357.4(CCDC115):​c.363C>A​(p.Asp121Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,432 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CCDC115 NM_032357.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.46

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC115	NM_032357.4	c.363C>A	p.Asp121Glu	missense_variant	Exon 4 of 5	ENST00000259229.7	NP_115733.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC115	ENST00000259229.7	c.363C>A	p.Asp121Glu	missense_variant	Exon 4 of 5	1	NM_032357.4	ENSP00000259229.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000800 AC: 2 AN: 250156 Hom.: 0 AF XY: 0.00000740 AC XY: 1 AN XY: 135214

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000328

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461432 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726946

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.60
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	0.010
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Benign	0.34	T;T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.58	T;T
M_CAP	Uncertain	0.27	D
MetaRNN	Uncertain	0.45	T;T
MetaSVM	Uncertain	0.48	D
MutationAssessor	Uncertain	2.8	M;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-2.9	D;D
REVEL	Uncertain	0.46
Sift	Uncertain	0.0060	D;D
Sift4G	Benign	0.14	T;T
Polyphen		0.39	B;P
Vest4		0.56
MutPred		0.31		Gain of sheet (P = 0.0827);.;
MVP		0.84
MPC		0.44
ClinPred		0.60	D
GERP RS		0.44
Varity_R		0.092
gMVP		0.65

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

LitVar

Other links and lift over

dbSNP: rs771683316; hg19: chr2-131098548;