6-24818557-A-G

Variant names:

• chr6-24818557-A-G
• rs9358802
• NM_001286445.3:c.2937T>C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0730

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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	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	Appris	UniProt
RIPOR2	ENST00000643898.2	c.2937T>C	p.Ala979Ala	synonymous_variant	Exon 20 of 22		NM_001286445.3	ENSP00000494268.2
RIPOR2	ENST00000259698.9	c.3000T>C	p.Ala1000Ala	synonymous_variant	Exon 21 of 23	1		ENSP00000259698.4
RIPOR2	ENST00000613507.4	c.3000T>C	p.Ala1000Ala	synonymous_variant	Exon 21 of 23	5		ENSP00000482957.1
RIPOR2	ENST00000538035.6	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.: 30

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

GnomAD3 exomes AF: 0.378 AC: 59163 AN: 156506 Hom.: 12350 AF XY: 0.379 AC XY: 31371 AN XY: 82800

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 SAS exome AF: 0.446

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.: 31 AF XY: 0.336 AC XY: 231096 AN XY: 688286

Gnomad4 AFR exome AF: 0.179

Gnomad4 AMR exome AF: 0.440

Gnomad4 ASJ exome AF: 0.261

Gnomad4 EAS exome AF: 0.664

Gnomad4 SAS exome AF: 0.448

Gnomad4 FIN exome AF: 0.396

Gnomad4 NFE exome AF: 0.313

Gnomad4 OTH exome AF: 0.337

GnomAD4 genome AF: 0.306 AC: 46500 AN: 151984 Hom.: 8023 Cov.: 30 AF XY: 0.315 AC XY: 23385 AN XY: 74256

Gnomad4 AFR AF: 0.187

Gnomad4 AMR AF: 0.375

Gnomad4 ASJ AF: 0.254

Gnomad4 EAS AF: 0.683

Gnomad4 SAS AF: 0.459

Gnomad4 FIN AF: 0.392

Gnomad4 NFE AF: 0.311

Gnomad4 OTH AF: 0.314

Alfa AF: 0.293 Hom.: 2916

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

Submissions by phenotype

not specified Benign:2

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). -

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. -

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
DANN	Benign	0.59

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

LitVar

Other links and lift over

dbSNP: rs9358802; hg19: chr6-24818785; COSMIC: COSV52418661;