6-24806454-T-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_001286445.3(RIPOR2):c.3063A>C(p.Ala1021=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000213 in 1,551,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00022 (0 hom.)
• Consequence: RIPOR2 NM_001286445.3 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.30

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 6-24806454-T-G is Benign according to our data. Variant chr6-24806454-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 2703036.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-24806454-T-G is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-2.3 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RIPOR2	NM_001286445.3	c.3063A>C	p.Ala1021=	synonymous_variant	22/22	ENST00000643898.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIPOR2	ENST00000643898.2	c.3063A>C	p.Ala1021=	synonymous_variant	22/22		NM_001286445.3	A2
RIPOR2	ENST00000259698.9	c.3126A>C	p.Ala1042=	synonymous_variant	23/23	1		A2
RIPOR2	ENST00000613507.4	c.3126A>C	p.Ala1042=	synonymous_variant	23/23	5		A2
RIPOR2	ENST00000538035.6	c.2976A>C	p.Ala992=	synonymous_variant	22/22	2		A2

Frequencies

GnomAD3 genomes AF: 0.000158 AC: 24 AN: 152248 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000723

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000220

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000203 AC: 32 AN: 157650 Hom.: 0 AF XY: 0.000216 AC XY: 18 AN XY: 83218

Gnomad AFR exome AF: 0.000122

Gnomad AMR exome AF: 0.000326

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000177

Gnomad NFE exome AF: 0.000293

Gnomad OTH exome AF: 0.000451

GnomAD4 exome AF: 0.000219 AC: 307 AN: 1399466 Hom.: 0 Cov.: 31 AF XY: 0.000222 AC XY: 153 AN XY: 690248

Gnomad4 AFR exome AF: 0.0000633

Gnomad4 AMR exome AF: 0.000309

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000126

Gnomad4 FIN exome AF: 0.000142

Gnomad4 NFE exome AF: 0.000254

Gnomad4 OTH exome AF: 0.000155

GnomAD4 genome AF: 0.000158 AC: 24 AN: 152366 Hom.: 0 Cov.: 33 AF XY: 0.000148 AC XY: 11 AN XY: 74508

Gnomad4 AFR AF: 0.0000721

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.000220

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000213 Hom.: 0

Bravo AF: 0.000147

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

RIPOR2-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 17, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Sep 21, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	0.80
Dann	Benign	0.43

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: rs369994154; hg19: chr6-24806682;