rs544443219

Variant names:

• chr2-170956457-C-G
• rs544443219
• NM_015530.5:c.721C>G

Your query was ambiguous. Multiple possible variants found:

• chr2-170956457-C-G
• chr2-170956457-C-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_015530.5(GORASP2):​c.721C>G​(p.Pro241Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000558 in 1,611,800 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000057 (0 hom.)
• Consequence: GORASP2 NM_015530.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.87
• 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.072993815).
• BS2: High AC in GnomAd4 at 7 AD gene.

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.721C>G	p.Pro241Ala	missense	Exon 7 of 10	NP_056345.3
	GORASP2	NM_001201428.2		c.517C>G	p.Pro173Ala	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.721C>G	p.Pro241Ala	missense	Exon 7 of 10	ENSP00000234160.4	Q9H8Y8-1
	GORASP2	ENST00000871667.1		c.721C>G	p.Pro241Ala	missense	Exon 7 of 10	ENSP00000541726.1
	GORASP2	ENST00000972174.1		c.718C>G	p.Pro240Ala	missense	Exon 7 of 10	ENSP00000642233.1

Frequencies

GnomAD3 genomes AF: 0.0000461 AC: 7 AN: 151788 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000144 AC: 36 AN: 250466 AF XY: 0.000111

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000638

Gnomad ASJ exome AF: 0.000893

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.0000569 AC: 83 AN: 1459894 Hom.: 0 Cov.: 29 AF XY: 0.0000578 AC XY: 42 AN XY: 726400

African (AFR) AF: 0.00 AC: 0 AN: 33420

American (AMR) AF: 0.000672 AC: 30 AN: 44620

Ashkenazi Jewish (ASJ) AF: 0.00103 AC: 27 AN: 26112

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86086

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52782

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.0000180 AC: 20 AN: 1111094

Other (OTH) AF: 0.0000829 AC: 5 AN: 60332

GnomAD4 genome AF: 0.0000461 AC: 7 AN: 151906 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74218

African (AFR) AF: 0.00 AC: 0 AN: 41446

American (AMR) AF: 0.000262 AC: 4 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4804

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10484

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67944

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000905 Hom.: 0

Bravo AF: 0.000110

ExAC AF: 0.0000988 AC: 12

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.059
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.073	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		3.9
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.15
Sift	Uncertain	0.022	D
Sift4G	Uncertain	0.060	T
Polyphen		0.18	B
Vest4		0.40
MutPred		0.58		Loss of sheet (P = 0.0104)
MVP		0.35
MPC		0.13
ClinPred		0.093	T
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.097
gMVP		0.64
Mutation Taster		=71/29	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs544443219; hg19: chr2-171812967;