2-170965956-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_015530.5(GORASP2):c.1185C>T(p.Ser395=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.916 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

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 -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.

Transcripts

RefSeq

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

Ensembl

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

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

GnomAD3 exomes AF: 0.920 AC: 231197 AN: 251308 Hom.: 107518 AF XY: 0.928 AC XY: 126005 AN XY: 135842

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 SAS exome AF: 0.982

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

Gnomad4 AFR exome AF: 0.566

Gnomad4 AMR exome AF: 0.927

Gnomad4 ASJ exome AF: 0.913

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.983

Gnomad4 FIN exome AF: 0.976

Gnomad4 NFE exome AF: 0.926

Gnomad4 OTH exome AF: 0.917

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

Gnomad4 AFR AF: 0.584

Gnomad4 AMR AF: 0.887

Gnomad4 ASJ AF: 0.909

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.982

Gnomad4 FIN AF: 0.978

Gnomad4 NFE AF: 0.931

Gnomad4 OTH AF: 0.852

Alfa AF: 0.924 Hom.: 94771

Bravo AF: 0.817

EpiCase AF: 0.926

EpiControl AF: 0.920

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
Cadd	Benign	0.89
Dann	Benign	0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6

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

Publications

LitVar

Other links and lift over

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