chr2-170956488-G-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4 BP6_Moderate

The NM_015530.5(GORASP2):​c.752G>A​(p.Gly251Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,613,142 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: GORASP2 NM_015530.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2790738).
• BP6: Variant 2-170956488-G-A is Benign according to our data. Variant chr2-170956488-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2292543.Status of the report is criteria_provided_single_submitter, 1 stars.

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>A	p.Gly251Glu	missense	Exon 7 of 10	NP_056345.3
	GORASP2	NM_001201428.2		c.548G>A	p.Gly183Glu	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>A	p.Gly251Glu	missense	Exon 7 of 10	ENSP00000234160.4	Q9H8Y8-1
	GORASP2	ENST00000871667.1		c.752G>A	p.Gly251Glu	missense	Exon 7 of 10	ENSP00000541726.1
	GORASP2	ENST00000972174.1		c.749G>A	p.Gly250Glu	missense	Exon 7 of 10	ENSP00000642233.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152082 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461060 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 726912

African (AFR) AF: 0.0000299 AC: 1 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: 0.00 AC: 0 AN: 5766

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

Other (OTH) AF: 0.0000331 AC: 2 AN: 60370

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152082 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74286

African (AFR) AF: 0.0000242 AC: 1 AN: 41398

American (AMR) AF: 0.00 AC: 0 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		6.6
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.20
Sift	Benign	0.15	T
Sift4G	Benign	0.20	T
Polyphen		0.92	P
Vest4		0.094
MutPred		0.47		Gain of solvent accessibility (P = 0.0145)
MVP		0.37
MPC		0.28
ClinPred		0.91	D
GERP RS		5.0
Varity_R		0.19
gMVP		0.54
Mutation Taster		=73/27	polymorphism

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

Other links and lift over

dbSNP: rs1444152035; hg19: chr2-171812998;