2-170966015-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_015530.5(GORASP2):c.1244C>T(p.Thr415Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00148 in 1,613,618 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0080 (17 hom., cov: 32)
  • Exomes 𝑓: 0.00081 (17 hom.)
• Consequence: GORASP2 NM_015530.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0250

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0024701357).
• BP6: Variant 2-170966015-C-T is Benign according to our data. Variant chr2-170966015-C-T is described in ClinVar as [Benign]. Clinvar id is 785017.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00797 (1213/152222) while in subpopulation AFR AF= 0.0273 (1134/41526). AF 95% confidence interval is 0.026. There are 17 homozygotes in gnomad4. There are 586 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 1211 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GORASP2	NM_015530.5	c.1244C>T	p.Thr415Met	missense_variant	10/10	ENST00000234160.5
GORASP2	NM_001201428.2	c.1040C>T	p.Thr347Met	missense_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GORASP2	ENST00000234160.5	c.1244C>T	p.Thr415Met	missense_variant	10/10	1	NM_015530.5	P1
GORASP2	ENST00000486498.1	n.1510C>T		non_coding_transcript_exon_variant	5/5	2
GORASP2	ENST00000442798.5	c.*1276C>T		3_prime_UTR_variant, NMD_transcript_variant	11/11	2

Frequencies

GnomAD3 genomes AF: 0.00796 AC: 1211 AN: 152104 Hom.: 17 Cov.: 32

Gnomad AFR AF: 0.0273

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00367

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00574

GnomAD3 exomes AF: 0.00223 AC: 561 AN: 251298 Hom.: 4 AF XY: 0.00156 AC XY: 212 AN XY: 135852

Gnomad AFR exome AF: 0.0310

Gnomad AMR exome AF: 0.00127

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.000807 AC: 1179 AN: 1461396 Hom.: 17 Cov.: 33 AF XY: 0.000690 AC XY: 502 AN XY: 727044

Gnomad4 AFR exome AF: 0.0291

Gnomad4 AMR exome AF: 0.00148

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.0000243

Gnomad4 OTH exome AF: 0.00161

GnomAD4 genome AF: 0.00797 AC: 1213 AN: 152222 Hom.: 17 Cov.: 32 AF XY: 0.00787 AC XY: 586 AN XY: 74436

Gnomad4 AFR AF: 0.0273

Gnomad4 AMR AF: 0.00366

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.00568

Alfa AF: 0.00145 Hom.: 4

Bravo AF: 0.00915

ESP6500AA AF: 0.0297 AC: 131

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00284 AC: 345

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.74
Cadd	Benign	7.4
Dann	Uncertain	0.99
DEOGEN2	Benign	0.021	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.67	T
MetaRNN	Benign	0.0025	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.13	N
REVEL	Benign	0.0080
Sift	Benign	0.17	T
Sift4G	Benign	0.10	T
Polyphen		0.0070	B
Vest4		0.14
MVP		0.13
MPC		0.14
ClinPred		0.0048	T
GERP RS		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.0085
gMVP		0.22

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: rs116256976; hg19: chr2-171822525; COSMIC: COSV52204130; COSMIC: COSV52204130;