2-170956555-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015530.5(GORASP2):​c.819T>G​(p.Ser273Arg) 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

GORASP2
NM_015530.5 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.787
Variant links:
Genes affected
GORASP2 (HGNC:17500): (golgi reassembly stacking protein 2) This gene encodes a member of the Golgi reassembly stacking protein family. These proteins may play a role in the stacking of Golgi cisternae and Golgi ribbon formation, as well as Golgi fragmentation during apoptosis or mitosis. The encoded protein also plays a role in the intracellular transport of transforming growth factor alpha and may function as a molecular chaperone. A pseudogene of this gene is located on the short arm of chromosome 2. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2011]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.16165167).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GORASP2NM_015530.5 linkc.819T>G p.Ser273Arg missense_variant Exon 7 of 10 ENST00000234160.5 NP_056345.3 Q9H8Y8-1
GORASP2NM_001201428.2 linkc.615T>G p.Ser205Arg missense_variant Exon 7 of 10 NP_001188357.1 Q9H8Y8-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GORASP2ENST00000234160.5 linkc.819T>G p.Ser273Arg missense_variant Exon 7 of 10 1 NM_015530.5 ENSP00000234160.4 Q9H8Y8-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
29
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.0000189

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 01, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.819T>G (p.S273R) alteration is located in exon 7 (coding exon 7) of the GORASP2 gene. This alteration results from a T to G substitution at nucleotide position 819, causing the serine (S) at amino acid position 273 to be replaced by an arginine (R). 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
Uncertain
0.42
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.45
CADD
Benign
18
DANN
Uncertain
0.99
DEOGEN2
Benign
0.045
T
Eigen
Benign
-0.24
Eigen_PC
Benign
-0.13
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Benign
0.85
D
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.16
T
MetaSVM
Benign
-0.97
T
MutationAssessor
Uncertain
2.1
M
PrimateAI
Uncertain
0.57
T
PROVEAN
Benign
-1.4
N
REVEL
Benign
0.14
Sift
Uncertain
0.0090
D
Sift4G
Benign
0.28
T
Polyphen
0.18
B
Vest4
0.34
MutPred
0.45
Loss of glycosylation at S273 (P = 0.0071);
MVP
0.29
MPC
0.16
ClinPred
0.35
T
GERP RS
2.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.18
gMVP
0.32

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs1162172252; hg19: chr2-171813065; API