rs756843533

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001286445.3(RIPOR2):c.3094T>C(p.Cys1032Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000251 in 1,551,722 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

RIPOR2
NM_001286445.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:3

Conservation

PhyloP100: 1.27

Publications

1 publications found

Variant links:

Genes affected

RIPOR2 (HGNC:13872): (RHO family interacting cell polarization regulator 2) This gene encodes an atypical inhibitor of the small G protein RhoA. Inhibition of RhoA activity by the encoded protein mediates myoblast fusion and polarization of T cells and neutrophils. The encoded protein is a component of hair cell stereocilia that is essential for hearing. A splice site mutation in this gene results in hearing loss in human patients. [provided by RefSeq, Sep 2016]

RIPOR2 Gene-Disease associations (from GenCC):

nonsyndromic genetic hearing loss
Inheritance: AR Classification: STRONG Submitted by: ClinGen
autosomal recessive nonsyndromic hearing loss 104
Inheritance: AR Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae)
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
autosomal dominant nonsyndromic hearing loss
Inheritance: AD Classification: LIMITED Submitted by: ClinGen
autosomal dominant nonsyndromic hearing loss 21
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

RIPOR2 links:

ENSG00000282804 (HGNC:):

ENSG00000282804 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.082796246).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286445.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RIPOR2	NM_001286445.3	MANE Select	c.3094T>C	p.Cys1032Arg	missense	Exon 22 of 22	NP_001273374.1	A0A2R8YEE0
RIPOR2	NM_014722.5		c.3157T>C	p.Cys1053Arg	missense	Exon 23 of 23	NP_055537.2
RIPOR2	NM_001346031.2		c.3007T>C	p.Cys1003Arg	missense	Exon 22 of 22	NP_001332960.1	F5GX51

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RIPOR2	ENST00000643898.2	MANE Select	c.3094T>C	p.Cys1032Arg	missense	Exon 22 of 22	ENSP00000494268.2	A0A2R8YEE0
RIPOR2	ENST00000259698.9	TSL:1	c.3157T>C	p.Cys1053Arg	missense	Exon 23 of 23	ENSP00000259698.4	Q9Y4F9-1
ENSG00000282804	ENST00000562221.1	TSL:5	c.133T>C	p.Cys45Arg	missense	Exon 2 of 3	ENSP00000455145.1	H3BP45

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.00

GnomAD2 exomes

AF:

0.0000191

AC:

AN:

157168

AF XY:

0.0000241

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000408

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000327

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000257

AC:

AN:

1399504

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

690270

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31596

American (AMR)

AF:

0.0000561

AC:

AN:

35682

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25178

East Asian (EAS)

AF:

0.00

AC:

AN:

35738

South Asian (SAS)

AF:

0.00

AC:

AN:

79192

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49368

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5700

European-Non Finnish (NFE)

AF:

0.0000315

AC:

AN:

1078972

Other (OTH)

AF:

0.00

AC:

AN:

58078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

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:

0.0000197

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41454

American (AMR)

AF:

0.0000655

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5202

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68040

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000579

Hom.:

Bravo

AF:

0.0000227

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.28

CADD

Benign

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.0077

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.54

M_CAP

Benign

0.010

MetaRNN

Benign

0.083

MetaSVM

Benign

-1.0

PhyloP100

1.3

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.6

REVEL

Benign

0.13

Sift

Benign

0.32

Sift4G

Benign

0.49

Polyphen

0.37

Vest4

0.20

MVP

0.59

MPC

0.53

ClinPred

0.040

GERP RS

2.3

Varity_R

0.17

gMVP

0.55

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over