9-128258048-C-T

Position:

• chr9-128258048-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001366244.2(GOLGA2):​c.2440G>A​(p.Gly814Arg) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GOLGA2 NM_001366244.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.41

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09975889).
• BP6: Variant 9-128258048-C-T is Benign according to our data. Variant chr9-128258048-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3100733.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GOLGA2	NM_001366244.2	c.2440G>A	p.Gly814Arg	missense_variant	23/27	ENST00000611957.5	NP_001353173.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GOLGA2	ENST00000611957.5	c.2440G>A	p.Gly814Arg	missense_variant	23/27	1	NM_001366244.2	ENSP00000478799.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 03, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	1.5
DANN	Benign	0.93
DEOGEN2	Benign	0.037	T;T;.;.;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.59	.;T;T;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.10	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;L;.;.;.
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-2.6	D;.;.;.;.
REVEL	Benign	0.038
Sift	Benign	0.23	T;.;.;.;.
Sift4G	Benign	0.17	T;T;T;T;.
Polyphen		0.78	P;P;.;.;.
Vest4		0.11
MutPred		0.18		Gain of solvent accessibility (P = 0.0674);Gain of solvent accessibility (P = 0.0674);.;.;.;
MVP		0.29
MPC		0.25
ClinPred		0.47	T
GERP RS		-3.6
Varity_R		0.12
gMVP		0.20

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-131020327;