rs4668356

Positions:

• chr2-170965956-C-G
• chr2-170965956-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_015530.5(GORASP2):​c.1185C>G​(p.Ser395=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00308 in 1,613,882 control chromosomes in the GnomAD database, including 12 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 0.0021 (0 hom., cov: 29)
  • Exomes 𝑓: 0.0032 (12 hom.)
• Consequence: GORASP2 NM_015530.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.387

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

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP7: Synonymous conserved (PhyloP=-0.387 with no splicing effect.
• BS2: High AC in GnomAd4 at 318 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GORASP2	NM_015530.5	c.1185C>G	p.Ser395=	synonymous_variant	10/10	ENST00000234160.5	NP_056345.3
GORASP2	NM_001201428.2	c.981C>G	p.Ser327=	synonymous_variant	10/10		NP_001188357.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GORASP2	ENST00000234160.5	c.1185C>G	p.Ser395=	synonymous_variant	10/10	1	NM_015530.5	ENSP00000234160	P1
GORASP2	ENST00000486498.1	n.1451C>G		non_coding_transcript_exon_variant	5/5	2
GORASP2	ENST00000442798.5	c.*1217C>G		3_prime_UTR_variant, NMD_transcript_variant	11/11	2		ENSP00000399889

Frequencies

GnomAD3 genomes AF: 0.00210 AC: 319 AN: 151908 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.000460

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.00197

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00357

Gnomad OTH AF: 0.00528

GnomAD3 exomes AF: 0.00223 AC: 561 AN: 251308 Hom.: 2 AF XY: 0.00216 AC XY: 294 AN XY: 135842

Gnomad AFR exome AF: 0.000554

Gnomad AMR exome AF: 0.00159

Gnomad ASJ exome AF: 0.00149

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.000370

Gnomad NFE exome AF: 0.00407

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.00318 AC: 4655 AN: 1461856 Hom.: 12 Cov.: 61 AF XY: 0.00309 AC XY: 2249 AN XY: 727224

Gnomad4 AFR exome AF: 0.000478

Gnomad4 AMR exome AF: 0.00174

Gnomad4 ASJ exome AF: 0.00249

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.000487

Gnomad4 NFE exome AF: 0.00387

Gnomad4 OTH exome AF: 0.00237

GnomAD4 genome AF: 0.00209 AC: 318 AN: 152026 Hom.: 0 Cov.: 29 AF XY: 0.00190 AC XY: 141 AN XY: 74324

Gnomad4 AFR AF: 0.000459

Gnomad4 AMR AF: 0.00196

Gnomad4 ASJ AF: 0.00230

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000377

Gnomad4 NFE AF: 0.00357

Gnomad4 OTH AF: 0.00522

Alfa AF: 0.000154 Hom.: 94771

EpiCase AF: 0.00382

EpiControl AF: 0.00462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	1.5
DANN	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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

Other links and lift over

dbSNP: rs4668356; hg19: chr2-171822466;