rs2207401

Variant names:

• chr6-24882753-C-T
• rs2207401
• NM_001286445.3:c.62-6936G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001286445.3(RIPOR2):​c.62-6936G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,168 control chromosomes in the GnomAD database, including 1,083 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.10 (1083 hom., cov: 32)
• Consequence: RIPOR2 NM_001286445.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38
• Publications: 1 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIPOR2	NM_001286445.3	c.62-6936G>A		intron_variant	Intron 1 of 21	ENST00000643898.2	NP_001273374.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIPOR2	ENST00000643898.2	c.62-6936G>A		intron_variant	Intron 1 of 21		NM_001286445.3	ENSP00000494268.2

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15521 AN: 152050 Hom.: 1081 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.0209

Gnomad AMR AF: 0.0727

Gnomad ASJ AF: 0.0833

Gnomad EAS AF: 0.0206

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.0334

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0668

Gnomad OTH AF: 0.114

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.102 AC: 15549 AN: 152168 Hom.: 1083 Cov.: 32 AF XY: 0.101 AC XY: 7502 AN XY: 74418

African (AFR) AF: 0.201 AC: 8354 AN: 41490

American (AMR) AF: 0.0726 AC: 1109 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0833 AC: 289 AN: 3470

East Asian (EAS) AF: 0.0204 AC: 106 AN: 5194

South Asian (SAS) AF: 0.104 AC: 500 AN: 4828

European-Finnish (FIN) AF: 0.0334 AC: 354 AN: 10594

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.0668 AC: 4542 AN: 67994

Other (OTH) AF: 0.113 AC: 238 AN: 2110

Alfa AF: 0.0766 Hom.: 360

Bravo AF: 0.109

Asia WGS AF: 0.0590 AC: 204 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	2.0
DANN	Benign	0.86
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2207401; hg19: chr6-24882981;