rs197922

Variant names:

• chr17-46931204-G-A
• rs197922
• NM_004287.5:c.200G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-46931204-G-A
• chr17-46931204-G-C
• chr17-46931204-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004287.5(GOSR2):​c.200G>A​(p.Arg67Lys) variant causes a missense change. The variant allele was found at a frequency of 0.343 in 1,435,212 control chromosomes in the GnomAD database, including 85,927 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R67Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.33 (8426 hom., cov: 32)
  • Exomes 𝑓: 0.34 (77501 hom.)
• Consequence: GOSR2 NM_004287.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:15
• Conservation: PhyloP100: 3.76
• Publications: 80 publications found

Genes affected

GOSR2 (HGNC:4431): (golgi SNAP receptor complex member 2) This gene encodes a trafficking membrane protein which transports proteins among the medial- and trans-Golgi compartments. Due to its chromosomal location and trafficking function, this gene may be involved in familial essential hypertension. [provided by RefSeq, Mar 2016]

ENSG00000262633 (HGNC:):

LRRC37A2 (HGNC:32404): (leucine rich repeat containing 37 member A2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017098784).
• BP6: Variant 17-46931204-G-A is Benign according to our data. Variant chr17-46931204-G-A is described in ClinVar as Benign. ClinVar VariationId is 129165.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004287.5. 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
	GOSR2	NM_004287.5	MANE Select	c.200G>A	p.Arg67Lys	missense	Exon 3 of 6	NP_004278.2
	GOSR2	NM_001321133.2		c.200G>A	p.Arg67Lys	missense	Exon 3 of 7	NP_001308062.1	I3NI02
	GOSR2	NM_054022.4		c.200G>A	p.Arg67Lys	missense	Exon 3 of 7	NP_473363.1	O14653-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOSR2	ENST00000640051.2	TSL:1 MANE Select	c.200G>A	p.Arg67Lys	missense	Exon 3 of 6	ENSP00000492751.1	O14653-1
	GOSR2	ENST00000225567.9	TSL:1	c.200G>A	p.Arg67Lys	missense	Exon 3 of 7	ENSP00000225567.4	O14653-2
	GOSR2	ENST00000640621.1	TSL:1	c.200G>A	p.Arg67Lys	missense	Exon 3 of 5	ENSP00000492830.1	O14653-3

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50302 AN: 151950 Hom.: 8433 Cov.: 32

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.328

GnomAD2 exomes AF: 0.346 AC: 86785 AN: 250870 AF XY: 0.351

Gnomad AFR exome AF: 0.300

Gnomad AMR exome AF: 0.296

Gnomad ASJ exome AF: 0.240

Gnomad EAS exome AF: 0.367

Gnomad FIN exome AF: 0.380

Gnomad NFE exome AF: 0.346

Gnomad OTH exome AF: 0.329

GnomAD4 exome AF: 0.345 AC: 442665 AN: 1283142 Hom.: 77501 Cov.: 20 AF XY: 0.348 AC XY: 225495 AN XY: 647642

African (AFR) AF: 0.294 AC: 8858 AN: 30120

American (AMR) AF: 0.298 AC: 13261 AN: 44492

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 6072 AN: 25096

East Asian (EAS) AF: 0.411 AC: 15973 AN: 38874

South Asian (SAS) AF: 0.428 AC: 35292 AN: 82534

European-Finnish (FIN) AF: 0.378 AC: 20175 AN: 53342

Middle Eastern (MID) AF: 0.275 AC: 1497 AN: 5448

European-Non Finnish (NFE) AF: 0.341 AC: 323641 AN: 948862

Other (OTH) AF: 0.329 AC: 17896 AN: 54374

GnomAD4 genome AF: 0.331 AC: 50313 AN: 152070 Hom.: 8426 Cov.: 32 AF XY: 0.335 AC XY: 24863 AN XY: 74326

African (AFR) AF: 0.296 AC: 12293 AN: 41476

American (AMR) AF: 0.307 AC: 4704 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 834 AN: 3466

East Asian (EAS) AF: 0.385 AC: 1991 AN: 5166

South Asian (SAS) AF: 0.450 AC: 2172 AN: 4826

European-Finnish (FIN) AF: 0.385 AC: 4059 AN: 10548

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.340 AC: 23092 AN: 67976

Other (OTH) AF: 0.329 AC: 694 AN: 2108

Alfa AF: 0.334 Hom.: 43667

Bravo AF: 0.320

TwinsUK AF: 0.344 AC: 1275

ALSPAC AF: 0.345 AC: 1329

ESP6500AA AF: 0.307 AC: 1354

ESP6500EA AF: 0.334 AC: 2870

ExAC AF: 0.349 AC: 42364

Asia WGS AF: 0.387 AC: 1349 AN: 3478

EpiCase AF: 0.338

EpiControl AF: 0.345

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	7	not specified (7)
-	-	3	not provided (3)
-	-	2	Progressive myoclonic epilepsy (2)
-	-	1	Inborn genetic diseases (1)
-	-	1	Myoclonic epilepsy, progressive, X-linked (1)
-	-	1	Progressive myoclonic epilepsy type 6 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	14
DANN	Benign	0.74
DEOGEN2	Benign	0.027	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.50	T
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-1.7	N
PhyloP100		3.8
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	2.4	N
REVEL	Benign	0.078
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.050
MPC		0.17
ClinPred		0.0082	T
GERP RS		4.8
PromoterAI		0.048	Neutral
Varity_R		0.12
gMVP		0.25
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: rs197922; hg19: chr17-45008570; COSMIC: COSV56661149; COSMIC: COSV56661149;