9-128258051-G-A

Position:

chr9-128258051-G-A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting

The NM_001366244.2(GOLGA2):c.2437C>T(p.Pro813Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000351 in 1,611,596 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00035 ( 0 hom. )

Consequence

GOLGA2
NM_001366244.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.171

Variant links:

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 links:

GOLGA2 (HGNC:):

GOLGA2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.048636436).

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000329 (50/152096) while in subpopulation NFE AF= 0.000515 (35/68002). AF 95% confidence interval is 0.00038. There are 0 homozygotes in gnomad4. There are 20 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GOLGA2	NM_001366244.2 linkuse as main transcript	c.2437C>T	p.Pro813Ser	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 linkuse as main transcript	c.2437C>T	p.Pro813Ser	missense_variant	23/27	1	NM_001366244.2	ENSP00000478799.2		A0A8J9BZL8

Frequencies

GnomAD3 genomes

AF:

0.000329

AC:

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000848

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000515

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000303

AC:

AN:

243826

Hom.:

AF XY:

0.000316

AC XY:

AN XY:

133072

show subpopulations

Gnomad AFR exome

AF:

0.0000694

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000734

Gnomad NFE exome

AF:

0.000499

Gnomad OTH exome

AF:

0.000335

GnomAD4 exome

AF:

0.000353

AC:

515

AN:

1459500

Hom.:

Cov.:

AF XY:

0.000350

AC XY:

254

AN XY:

726110

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.0000672

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.000988

Gnomad4 NFE exome

AF:

0.000397

Gnomad4 OTH exome

AF:

0.000282

GnomAD4 genome

AF:

0.000329

AC:

AN:

152096

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000848

Gnomad4 NFE

AF:

0.000515

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000251

Hom.:

Bravo

AF:

0.000276

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000118

AC:

ExAC

AF:

0.000405

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000474

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 21, 2024

The c.2356C>T (p.P786S) alteration is located in exon 22 (coding exon 22) of the GOLGA2 gene. This alteration results from a C to T substitution at nucleotide position 2356, causing the proline (P) at amino acid position 786 to be replaced by a serine (S). 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

0.088

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.41

CADD

Benign

0.69

DANN

Uncertain

0.99

DEOGEN2

Benign

0.036

T;T;.;.;.

Eigen

Benign

-0.94

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.057

LIST_S2

Benign

0.62

.;T;T;T;T

M_CAP

Benign

0.037

MetaRNN

Benign

0.049

T;T;T;T;T

MetaSVM

Uncertain

-0.27

MutationAssessor

Uncertain

2.0

M;M;.;.;.

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-3.5

D;.;.;.;.

REVEL

Benign

0.25

Sift

Benign

0.11

T;.;.;.;.

Sift4G

Uncertain

0.054

T;T;T;D;.

Polyphen

1.0

D;D;.;.;.

Vest4

0.11

MVP

0.70

MPC

0.22

ClinPred

0.11

GERP RS

-1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.065

gMVP

0.16

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over