9-128257399-G-C

Position:

• chr9-128257399-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001366244.2(GOLGA2):​c.2845C>G​(p.Gln949Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,460,728 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: GOLGA2 NM_001366244.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.60

Genes affected

GOLGA2 (HGNC:4425): (golgin A2) The Golgi apparatus, which participates in glycosylation and transport of proteins and lipids in the secretory pathway, consists of a series of stacked cisternae (flattened membrane sacs). Interactions between the Golgi and microtubules are thought to be important for the reorganization of the Golgi after it fragments during mitosis. This gene encodes one of the golgins, a family of proteins localized to the Golgi. This encoded protein has been postulated to play roles in the stacking of Golgi cisternae and in vesicular transport. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of these variants has not been determined. [provided by RefSeq, Feb 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17990309).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOLGA2	NM_001366244.2	c.2845C>G	p.Gln949Glu	missense_variant	Exon 26 of 27	ENST00000611957.5	NP_001353173.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GOLGA2	ENST00000611957.5	c.2845C>G	p.Gln949Glu	missense_variant	Exon 26 of 27	1	NM_001366244.2	ENSP00000478799.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1460728 Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4 AN XY: 726668

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000450

Gnomad4 OTH exome AF: 0.00

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

Oct 20, 2023

The c.2764C>G (p.Q922E) alteration is located in exon 25 (coding exon 25) of the GOLGA2 gene. This alteration results from a C to G substitution at nucleotide position 2764, causing the glutamine (Q) at amino acid position 922 to be replaced by a glutamic acid (E). 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	0.070
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	9.8
DANN	Benign	0.95
DEOGEN2	Benign	0.013	T;T;.;.
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.71	.;T;T;T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.18	T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Pathogenic	3.1	M;M;.;.
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.3	N;.;.;.
REVEL	Benign	0.068
Sift	Benign	0.18	T;.;.;.
Sift4G	Uncertain	0.057	T;T;T;T
Polyphen		0.22	B;B;.;.
Vest4		0.30
MutPred		0.32		Gain of glycosylation at P921 (P = 0.091);Gain of glycosylation at P921 (P = 0.091);.;.;
MVP		0.46
MPC		0.24
ClinPred		0.26	T
GERP RS		3.9
Varity_R		0.066
gMVP		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs199663736; hg19: chr9-131019678;