Genetic Variant RALGPS2:p.Thr16Ile (chr1-178776811-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_152663.5(RALGPS2):c.47C>T(p.Thr16Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000229 in 1,612,742 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

RALGPS2
NM_152663.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.69

Publications

0 publications found

Variant links:

Genes affected

RALGPS2 (HGNC:30279): (Ral GEF with PH domain and SH3 binding motif 2) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of Ral protein signal transduction; regulation of catalytic activity; and small GTPase mediated signal transduction. Predicted to be located in cytoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

RALGPS2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.020262033).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152663.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RALGPS2	NM_152663.5	MANE Select	c.47C>T	p.Thr16Ile	missense	Exon 2 of 20	NP_689876.2
RALGPS2	NM_001286247.2		c.47C>T	p.Thr16Ile	missense	Exon 2 of 19	NP_001273176.1	Q86X27-3
RALGPS2	NM_001400042.1		c.47C>T	p.Thr16Ile	missense	Exon 2 of 19	NP_001386971.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RALGPS2	ENST00000367635.8	TSL:1 MANE Select	c.47C>T	p.Thr16Ile	missense	Exon 2 of 20	ENSP00000356607.3	Q86X27-1
RALGPS2	ENST00000853433.1		c.47C>T	p.Thr16Ile	missense	Exon 2 of 20	ENSP00000523492.1
RALGPS2	ENST00000853430.1		c.47C>T	p.Thr16Ile	missense	Exon 2 of 20	ENSP00000523489.1

Frequencies

GnomAD3 genomes

AF:

0.0000855

AC:

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00212

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000679

AC:

AN:

250464

AF XY:

0.0000591

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000929

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000164

AC:

AN:

1460524

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

726614

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33432

American (AMR)

AF:

0.00

AC:

AN:

44636

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26104

East Asian (EAS)

AF:

0.000404

AC:

AN:

39620

South Asian (SAS)

AF:

0.00

AC:

AN:

86106

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53360

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.00000630

AC:

AN:

1111192

Other (OTH)

AF:

0.0000166

AC:

AN:

60320

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000854

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41544

American (AMR)

AF:

0.00

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00213

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68010

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000712

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.0000330

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.038

Eigen

Benign

-0.088

Eigen_PC

Benign

0.10

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.80

M_CAP

Benign

0.0068

MetaRNN

Benign

0.020

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

PhyloP100

3.7

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.3

REVEL

Benign

0.023

Sift

Benign

0.044

Sift4G

Benign

0.25

Polyphen

0.18

Vest4

0.30

MutPred

0.24

Gain of helix (P = 0.0325)

MVP

0.082

MPC

0.49

ClinPred

0.12

GERP RS

5.2

Varity_R

0.12

gMVP

0.49

Mutation Taster

=71/29

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