rs114812653

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_004761.5(RGL2):c.1766G>C(p.Ser589Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00101 in 1,547,910 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0059 ( 12 hom., cov: 32)

Exomes 𝑓: 0.00048 ( 8 hom. )

Consequence

RGL2
NM_004761.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.70

Publications

0 publications found

Variant links:

Genes affected

RGL2 (HGNC:9769): (ral guanine nucleotide dissociation stimulator like 2) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of catalytic activity and small GTPase mediated signal transduction. Predicted to act upstream of or within negative regulation of cardiac muscle cell apoptotic process; positive regulation of phosphatidylinositol 3-kinase signaling; and regulation of Ral protein signal transduction. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

RGL2 links:

PFDN6 (HGNC:4926): (prefoldin subunit 6) PFDN6 is a subunit of the heteromeric prefoldin complex that chaperones nascent actin (see MIM 102560) and alpha- and beta-tubulin (see MIM 602529 and MIM 191130, respectively) chains pending their transfer to the cytosolic chaperonin containing TCP1 (MIM 186980) (CCT) complex (Hansen et al., 1999 [PubMed 10209023]).[supplied by OMIM, Jul 2010]

PFDN6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0029233098).

BP6

Variant 6-33293257-C-G is Benign according to our data. Variant chr6-33293257-C-G is described in ClinVar as Benign. ClinVar VariationId is 784072.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00587 (894/152356) while in subpopulation AFR AF = 0.0208 (865/41588). AF 95% confidence interval is 0.0196. There are 12 homozygotes in GnomAd4. There are 428 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 12 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004761.5. 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
	RGL2	NM_004761.5	MANE Select	c.1766G>C	p.Ser589Thr	missense	Exon 16 of 18	NP_004752.1	A0A024RCS9
	RGL2	NM_001243738.2		c.1520G>C	p.Ser507Thr	missense	Exon 15 of 17	NP_001230667.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RGL2	ENST00000497454.6	TSL:1 MANE Select	c.1766G>C	p.Ser589Thr	missense	Exon 16 of 18	ENSP00000420211.1	O15211-1
RGL2	ENST00000437840.6	TSL:1	n.1671G>C		non_coding_transcript_exon	Exon 15 of 17
RGL2	ENST00000968840.1		c.1826G>C	p.Ser609Thr	missense	Exon 16 of 18	ENSP00000638899.1

Frequencies

GnomAD3 genomes

AF:

0.00587

AC:

894

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0209

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00382

GnomAD2 exomes

AF:

0.00169

AC:

323

AN:

191644

AF XY:

0.00120

show subpopulations

Gnomad AFR exome

AF:

0.0199

Gnomad AMR exome

AF:

0.000396

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000112

Gnomad OTH exome

AF:

0.000449

GnomAD4 exome

AF:

0.000484

AC:

676

AN:

1395554

Hom.:

Cov.:

AF XY:

0.000395

AC XY:

272

AN XY:

687818

show subpopulations

African (AFR)

AF:

0.0193

AC:

605

AN:

31386

American (AMR)

AF:

0.000540

AC:

AN:

35182

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21100

East Asian (EAS)

AF:

0.00

AC:

AN:

39288

South Asian (SAS)

AF:

0.00

AC:

AN:

74972

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50136

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5406

European-Non Finnish (NFE)

AF:

0.00000278

AC:

AN:

1080636

Other (OTH)

AF:

0.000853

AC:

AN:

57448

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

127

170

212

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00587

AC:

894

AN:

152356

Hom.:

Cov.:

AF XY:

0.00574

AC XY:

428

AN XY:

74502

show subpopulations

African (AFR)

AF:

0.0208

AC:

865

AN:

41588

American (AMR)

AF:

0.00124

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68044

Other (OTH)

AF:

0.00378

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

136

182

227

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00114

Hom.:

Bravo

AF:

0.00691

ESP6500AA

AF:

0.0207

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00193

AC:

233

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.77

CADD

Benign

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.027

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.13

MetaRNN

Benign

0.0029

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.65

PhyloP100

2.7

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.3

REVEL

Benign

0.049

Sift

Benign

0.68

Sift4G

Benign

0.42

Polyphen

0.0

Vest4

0.052

MVP

0.33

MPC

0.32

ClinPred

0.014

GERP RS

3.6

Varity_R

0.071

gMVP

0.35

Mutation Taster

=95/5

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over