2-130339179-G-C

Variant names:

• chr2-130339179-G-C
• rs772966334
• NM_032357.4:c.484C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032357.4(VMA22):​c.484C>G​(p.Arg162Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000267 in 1,461,840 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.000027 (0 hom.)
• Consequence: VMA22 NM_032357.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.26
• Publications: 0 publications found

Genes affected

VMA22 (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]

VMA22 Gene-Disease associations (from GenCC):

• CCDC115-CDG

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: ClinGen, Laboratory for Molecular Medicine, Orphanet, G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3076569).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032357.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VMA22	NM_032357.4	MANE Select	c.484C>G	p.Arg162Gly	missense	Exon 5 of 5	NP_115733.2
	VMA22	NM_001321118.1		c.469C>G	p.Arg157Gly	missense	Exon 5 of 5	NP_001308047.1	B8ZZ99
	VMA22	NM_001321119.2		c.460C>G	p.Arg154Gly	missense	Exon 5 of 5	NP_001308048.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VMA22	ENST00000259229.7	TSL:1 MANE Select	c.484C>G	p.Arg162Gly	missense	Exon 5 of 5	ENSP00000259229.2	Q96NT0-1
	VMA22	ENST00000902736.1		c.610C>G	p.Arg204Gly	missense	Exon 6 of 6	ENSP00000572795.1
	VMA22	ENST00000409127.1	TSL:2	c.469C>G	p.Arg157Gly	missense	Exon 5 of 5	ENSP00000387301.1	B8ZZ99

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000358 AC: 9 AN: 251328 AF XY: 0.0000221

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000267 AC: 39 AN: 1461840 Hom.: 0 Cov.: 30 AF XY: 0.0000248 AC XY: 18 AN XY: 727216

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000151 AC: 13 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.0000216 AC: 24 AN: 1112002

Other (OTH) AF: 0.0000331 AC: 2 AN: 60396

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000412 AC: 5

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Uncertain	-0.010
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T
Eigen	Benign	0.051
Eigen_PC	Benign	0.024
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.72	T
M_CAP	Pathogenic	0.48	D
MetaRNN	Benign	0.31	T
MetaSVM	Pathogenic	0.96	D
MutationAssessor	Uncertain	2.6	M
PhyloP100		2.3
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-3.6	D
REVEL	Uncertain	0.49
Sift	Uncertain	0.020	D
Sift4G	Benign	0.063	T
Polyphen		0.63	P
Vest4		0.34
MutPred		0.32		Loss of MoRF binding (P = 0.0224)
MVP		0.98
MPC		0.66
ClinPred		0.53	D
GERP RS		3.1
Varity_R		0.22
gMVP		0.63
Mutation Taster		=91/9	polymorphism

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: rs772966334; hg19: chr2-131096752;