chr2-170956485-C-A

Variant names:

• chr2-170956485-C-A
• rs773448196
• NM_015530.5:c.749C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015530.5(GORASP2):​c.749C>A​(p.Thr250Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. T250I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GORASP2 NM_015530.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.99
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23418689).

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.749C>A	p.Thr250Lys	missense	Exon 7 of 10	NP_056345.3
	GORASP2	NM_001201428.2		c.545C>A	p.Thr182Lys	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.749C>A	p.Thr250Lys	missense	Exon 7 of 10	ENSP00000234160.4	Q9H8Y8-1
	GORASP2	ENST00000871667.1		c.749C>A	p.Thr250Lys	missense	Exon 7 of 10	ENSP00000541726.1
	GORASP2	ENST00000972174.1		c.746C>A	p.Thr249Lys	missense	Exon 7 of 10	ENSP00000642233.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.082	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.10	T
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		5.0
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.15
Sift	Uncertain	0.020	D
Sift4G	Benign	0.62	T
Polyphen		0.49	P
Vest4		0.24
MutPred		0.57		Gain of solvent accessibility (P = 0.0038)
MVP		0.26
MPC		0.17
ClinPred		0.76	D
GERP RS		5.9
Varity_R		0.13
gMVP		0.57
Mutation Taster		=61/39	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: rs773448196; hg19: chr2-171812995;