9-128275954-G-A

Variant names:

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

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>T​(p.Pro8Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000097 in 1,443,468 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. P8R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000097 (0 hom.)
• 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=0.29967767).

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>T	p.Pro8Leu	missense	Exon 1 of 27	NP_001353173.2	A0A8J9BZL8
	GOLGA2	NM_001389695.2		c.23C>T	p.Pro8Leu	missense	Exon 1 of 27	NP_001376624.2
	GOLGA2	NM_001389696.2		c.23C>T	p.Pro8Leu	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>T	p.Pro8Leu	missense	Exon 1 of 27	ENSP00000478799.2	A0A8J9BZL8
	GOLGA2	ENST00000421699.8	TSL:1	c.23C>T	p.Pro8Leu	missense	Exon 1 of 26	ENSP00000416097.4	Q08379-1
	GOLGA2	ENST00000964637.1		c.23C>T	p.Pro8Leu	missense	Exon 1 of 27	ENSP00000634696.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000866 AC: 2 AN: 230836 AF XY: 0.00000789

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000605

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000945

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000970 AC: 14 AN: 1443468 Hom.: 0 Cov.: 30 AF XY: 0.0000111 AC XY: 8 AN XY: 718474

African (AFR) AF: 0.00 AC: 0 AN: 32410

American (AMR) AF: 0.00 AC: 0 AN: 39374

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25496

East Asian (EAS) AF: 0.00 AC: 0 AN: 39220

South Asian (SAS) AF: 0.00 AC: 0 AN: 85212

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52980

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5544

European-Non Finnish (NFE) AF: 0.0000127 AC: 14 AN: 1103648

Other (OTH) AF: 0.00 AC: 0 AN: 59584

GnomAD4 genome Cov.: 32

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	0.20
BayesDel_addAF	Benign	-0.057	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.098	T
Eigen	Benign	0.087
Eigen_PC	Benign	-0.063
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.056	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.86	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		0.96	D
Vest4		0.48
MutPred		0.22		Loss of glycosylation at P8 (P = 0.008)
MVP		0.53
MPC		0.26
ClinPred		0.87	D
GERP RS		2.7
PromoterAI		-0.0035	Neutral
Varity_R		0.21
gMVP		0.26
Mutation Taster		=89/11	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;