6-24818557-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001286445.3(RIPOR2):c.2937T>C(p.Ala979Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 1,547,186 control chromosomes in the GnomAD database, including 89,341 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 8023 hom., cov: 30)

Exomes 𝑓: 0.33 ( 81318 hom. )

Consequence

RIPOR2
NM_001286445.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0730

Publications

17 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):

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

RIPOR2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 6-24818557-A-G is Benign according to our data. Variant chr6-24818557-A-G is described in ClinVar as Benign. ClinVar VariationId is 508096.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.073 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIPOR2	NM_001286445.3 link	c.2937T>C	p.Ala979Ala	synonymous_variant	Exon 20 of 22	ENST00000643898.2	NP_001273374.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
RIPOR2	ENST00000643898.2 link	c.2937T>C	p.Ala979Ala	synonymous_variant	Exon 20 of 22		NM_001286445.3	ENSP00000494268.2
RIPOR2	ENST00000259698.9 link	c.3000T>C	p.Ala1000Ala	synonymous_variant	Exon 21 of 23	1		ENSP00000259698.4
RIPOR2	ENST00000613507.4 link	c.3000T>C	p.Ala1000Ala	synonymous_variant	Exon 21 of 23	5		ENSP00000482957.1
RIPOR2	ENST00000538035.6 link	c.2850T>C	p.Ala950Ala	synonymous_variant	Exon 20 of 22	2		ENSP00000441138.2

Frequencies

GnomAD3 genomes

AF:

0.306

AC:

46460

AN:

151866

Hom.:

8017

Cov.:

show subpopulations

Gnomad AFR

AF:

0.187

Gnomad AMI

AF:

0.485

Gnomad AMR

AF:

0.375

Gnomad ASJ

AF:

0.254

Gnomad EAS

AF:

0.684

Gnomad SAS

AF:

0.458

Gnomad FIN

AF:

0.392

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.311

Gnomad OTH

AF:

0.310

GnomAD2 exomes

AF:

0.378

AC:

59163

AN:

156506

AF XY:

0.379

show subpopulations

Gnomad AFR exome

AF:

0.188

Gnomad AMR exome

AF:

0.455

Gnomad ASJ exome

AF:

0.260

Gnomad EAS exome

AF:

0.686

Gnomad FIN exome

AF:

0.395

Gnomad NFE exome

AF:

0.306

Gnomad OTH exome

AF:

0.338

GnomAD4 exome

AF:

0.332

AC:

463697

AN:

1395202

Hom.:

81318

Cov.:

AF XY:

0.336

AC XY:

231096

AN XY:

688286

show subpopulations

African (AFR)

AF:

0.179

AC:

5660

AN:

31544

American (AMR)

AF:

0.440

AC:

15649

AN:

35600

Ashkenazi Jewish (ASJ)

AF:

0.261

AC:

6549

AN:

25088

East Asian (EAS)

AF:

0.664

AC:

23705

AN:

35690

South Asian (SAS)

AF:

0.448

AC:

35266

AN:

78758

European-Finnish (FIN)

AF:

0.396

AC:

19491

AN:

49210

Middle Eastern (MID)

AF:

0.251

AC:

1421

AN:

5658

European-Non Finnish (NFE)

AF:

0.313

AC:

336464

AN:

1075844

Other (OTH)

AF:

0.337

AC:

19492

AN:

57810

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

13441

26882

40323

53764

67205

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11356

22712

34068

45424

56780

<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:

0.306

AC:

46500

AN:

151984

Hom.:

8023

Cov.:

AF XY:

0.315

AC XY:

23385

AN XY:

74256

show subpopulations

African (AFR)

AF:

0.187

AC:

7763

AN:

41496

American (AMR)

AF:

0.375

AC:

5731

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.254

AC:

882

AN:

3470

East Asian (EAS)

AF:

0.683

AC:

3496

AN:

5116

South Asian (SAS)

AF:

0.459

AC:

2207

AN:

4808

European-Finnish (FIN)

AF:

0.392

AC:

4142

AN:

10554

Middle Eastern (MID)

AF:

0.241

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.311

AC:

21105

AN:

67956

Other (OTH)

AF:

0.314

AC:

662

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1511

3022

4532

6043

7554

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

470

940

1410

1880

2350

<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:

0.292

Hom.:

2928

Bravo

AF:

0.300

Asia WGS

AF:

0.542

AC:

1881

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

May 09, 2017

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

Aug 23, 2017

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

p.Ala1000Ala in exon 21 of FAM65B: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located wi thin the splice consensus sequence, and has been identified in 67.95% (424/624) of East Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac .broadinstitute.org; dbSNP rs9358802).

not provided

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

7.8

(source)

DANN

Benign

0.59

PhyloP100

-0.073

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over