9-128275954-G-C

Variant names:

• chr9-128275954-G-C
• rs1392278112
• NM_001366244.2:c.23C>G

Variant summary

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

The NM_001366244.2(GOLGA2):​c.23C>G​(p.Pro8Arg) variant causes a missense change. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P8L) has been classified 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: 3.96
• Publications: 1 publications found

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]

SWI5 (HGNC:31412): (SWI5 homologous recombination repair protein) Involved in cellular response to ionizing radiation and double-strand break repair via homologous recombination. Part of Swi5-Sfr1 complex. [provided by Alliance of Genome Resources, Apr 2022]

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=0.3252594).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366244.2. 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
	GOLGA2	NM_001366244.2	MANE Select	c.23C>G	p.Pro8Arg	missense	Exon 1 of 27	NP_001353173.2	A0A8J9BZL8
	GOLGA2	NM_001389695.2		c.23C>G	p.Pro8Arg	missense	Exon 1 of 27	NP_001376624.2
	GOLGA2	NM_001389696.2		c.23C>G	p.Pro8Arg	missense	Exon 1 of 27	NP_001376625.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOLGA2	ENST00000611957.5	TSL:1 MANE Select	c.23C>G	p.Pro8Arg	missense	Exon 1 of 27	ENSP00000478799.2	A0A8J9BZL8
	GOLGA2	ENST00000421699.8	TSL:1	c.23C>G	p.Pro8Arg	missense	Exon 1 of 26	ENSP00000416097.4	Q08379-1
	GOLGA2	ENST00000964637.1		c.23C>G	p.Pro8Arg	missense	Exon 1 of 27	ENSP00000634696.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	23
DANN	Benign	0.97
DEOGEN2	Benign	0.098	T
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.015
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.061	D
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.74	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		4.0
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.18
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.51
MutPred		0.30		Gain of MoRF binding (P = 0.0016)
MVP		0.46
MPC		0.74
ClinPred		0.96	D
GERP RS		2.7
PromoterAI		-0.0015	Neutral
Varity_R		0.33
gMVP		0.29
Mutation Taster		=90/10	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: rs1392278112; hg19: chr9-131038233;