chr2-170956488-G-T

Variant names:

• chr2-170956488-G-T
• rs1444152035
• NM_015530.5:c.752G>T

Variant summary

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

The NM_015530.5(GORASP2):​c.752G>T​(p.Gly251Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G251E) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: GORASP2 NM_015530.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.55
• Publications: 0 publications found

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]

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=0.33508545).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015530.5. 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
	GORASP2	NM_015530.5	MANE Select	c.752G>T	p.Gly251Val	missense	Exon 7 of 10	NP_056345.3
	GORASP2	NM_001201428.2		c.548G>T	p.Gly183Val	missense	Exon 7 of 10	NP_001188357.1	Q9H8Y8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GORASP2	ENST00000234160.5	TSL:1 MANE Select	c.752G>T	p.Gly251Val	missense	Exon 7 of 10	ENSP00000234160.4	Q9H8Y8-1
	GORASP2	ENST00000871667.1		c.752G>T	p.Gly251Val	missense	Exon 7 of 10	ENSP00000541726.1
	GORASP2	ENST00000972174.1		c.749G>T	p.Gly250Val	missense	Exon 7 of 10	ENSP00000642233.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461060 Hom.: 0 Cov.: 29 AF XY: 0.00000275 AC XY: 2 AN XY: 726912

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33448

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53312

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111390

Other (OTH) AF: 0.00 AC: 0 AN: 60370

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0385499), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.085	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.77	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		6.6
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.24
Sift	Benign	0.091	T
Sift4G	Benign	0.13	T
Polyphen		0.92	P
Vest4		0.23
MutPred		0.42		Gain of sheet (P = 0.0101)
MVP		0.45
MPC		0.18
ClinPred		0.95	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.22
gMVP		0.59
Mutation Taster		=76/24	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: rs1444152035; hg19: chr2-171812998;