9-128257454-G-C

Position:

• chr9-128257454-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001366244.2(GOLGA2):​c.2790C>G​(p.Phe930Leu) 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 benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GOLGA2 NM_001366244.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.266

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]

GOLGA2 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37541443).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GOLGA2	NM_001366244.2	c.2790C>G	p.Phe930Leu	missense_variant	26/27	ENST00000611957.5	NP_001353173.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GOLGA2	ENST00000611957.5	c.2790C>G	p.Phe930Leu	missense_variant	26/27	1	NM_001366244.2	ENSP00000478799.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Apr 24, 2024

The c.2709C>G (p.F903L) 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 2709, causing the phenylalanine (F) at amino acid position 903 to be replaced by a leucine (L). 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	Pathogenic	0.87
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.045	T;T;.;.
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.50	N
LIST_S2	Benign	0.77	.;T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.38	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M;M;.;.
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-3.4	D;.;.;.
REVEL	Benign	0.065
Sift	Benign	0.060	T;.;.;.
Sift4G	Benign	0.11	T;T;T;T
Polyphen		1.0	D;D;.;.
Vest4		0.17
MutPred		0.65		Gain of disorder (P = 0.0425);Gain of disorder (P = 0.0425);.;.;
MVP		0.53
MPC		0.25
ClinPred		0.72	D
GERP RS		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.16
gMVP		0.44

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: rs774799443; hg19: chr9-131019733;