2-170965956-C-T

Variant names:

• chr2-170965956-C-T
• rs4668356
• NM_015530.5:c.1185C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_015530.5(GORASP2):​c.1185C>T​(p.Ser395Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.916 in 1,613,776 control chromosomes in the GnomAD database, including 682,802 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.84 (55207 hom., cov: 29)
  • Exomes 𝑓: 0.92 (627595 hom.)
• Consequence: GORASP2 NM_015530.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.387
• Publications: 27 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP7: Synonymous conserved (PhyloP=-0.387 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

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.1185C>T	p.Ser395Ser	synonymous	Exon 10 of 10	NP_056345.3
	GORASP2	NM_001201428.2		c.981C>T	p.Ser327Ser	synonymous	Exon 10 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.1185C>T	p.Ser395Ser	synonymous	Exon 10 of 10	ENSP00000234160.4	Q9H8Y8-1
	GORASP2	ENST00000871667.1		c.1203C>T	p.Ser401Ser	synonymous	Exon 10 of 10	ENSP00000541726.1
	GORASP2	ENST00000972174.1		c.1182C>T	p.Ser394Ser	synonymous	Exon 10 of 10	ENSP00000642233.1

Frequencies

GnomAD3 genomes AF: 0.837 AC: 127146 AN: 151860 Hom.: 55177 Cov.: 29

Gnomad AFR AF: 0.584

Gnomad AMI AF: 0.822

Gnomad AMR AF: 0.887

Gnomad ASJ AF: 0.909

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.982

Gnomad FIN AF: 0.978

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.931

Gnomad OTH AF: 0.851

GnomAD2 exomes AF: 0.920 AC: 231197 AN: 251308 AF XY: 0.928

Gnomad AFR exome AF: 0.570

Gnomad AMR exome AF: 0.931

Gnomad ASJ exome AF: 0.914

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.978

Gnomad NFE exome AF: 0.926

Gnomad OTH exome AF: 0.924

GnomAD4 exome AF: 0.925 AC: 1351768 AN: 1461798 Hom.: 627595 Cov.: 61 AF XY: 0.928 AC XY: 674881 AN XY: 727198

African (AFR) AF: 0.566 AC: 18939 AN: 33478

American (AMR) AF: 0.927 AC: 41466 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.913 AC: 23863 AN: 26136

East Asian (EAS) AF: 1.00 AC: 39697 AN: 39700

South Asian (SAS) AF: 0.983 AC: 84756 AN: 86256

European-Finnish (FIN) AF: 0.976 AC: 52124 AN: 53396

Middle Eastern (MID) AF: 0.937 AC: 5405 AN: 5768

European-Non Finnish (NFE) AF: 0.926 AC: 1030138 AN: 1111946

Other (OTH) AF: 0.917 AC: 55380 AN: 60394

GnomAD4 genome AF: 0.837 AC: 127223 AN: 151978 Hom.: 55207 Cov.: 29 AF XY: 0.844 AC XY: 62690 AN XY: 74300

African (AFR) AF: 0.584 AC: 24142 AN: 41352

American (AMR) AF: 0.887 AC: 13549 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.909 AC: 3157 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5136 AN: 5138

South Asian (SAS) AF: 0.982 AC: 4735 AN: 4822

European-Finnish (FIN) AF: 0.978 AC: 10365 AN: 10596

Middle Eastern (MID) AF: 0.891 AC: 262 AN: 294

European-Non Finnish (NFE) AF: 0.931 AC: 63334 AN: 68012

Other (OTH) AF: 0.852 AC: 1795 AN: 2106

Alfa AF: 0.916 Hom.: 131058

Bravo AF: 0.817

EpiCase AF: 0.926

EpiControl AF: 0.920

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.89
DANN	Benign	0.69
PhyloP100		-0.39
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Mutation Taster		=100/0	polymorphism (auto)

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: rs4668356; hg19: chr2-171822466; COSMIC: COSV52203185; COSMIC: COSV52203185;