chr6-24899340-C-A

Variant names:

• chr6-24899340-C-A
• rs2817723
• NM_001286445.3:c.62-23523G>T

Variant summary

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

The NM_001286445.3(RIPOR2):​c.62-23523G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 151,964 control chromosomes in the GnomAD database, including 17,344 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 0.46 (17344 hom., cov: 32)
• Consequence: RIPOR2 NM_001286445.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.392
• Publications: 0 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):

• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.619 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIPOR2	NM_001286445.3	MANE Select	c.62-23523G>T		intron	N/A	NP_001273374.1	A0A2R8YEE0
	RIPOR2	NM_014722.5		c.-27+11478G>T		intron	N/A	NP_055537.2
	RIPOR2	NM_001346031.2		c.-27+11478G>T		intron	N/A	NP_001332960.1	F5GX51

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIPOR2	ENST00000643898.2	MANE Select	c.62-23523G>T		intron	N/A	ENSP00000494268.2	A0A2R8YEE0
	RIPOR2	ENST00000259698.9	TSL:1	c.-27+11478G>T		intron	N/A	ENSP00000259698.4	Q9Y4F9-1
	RIPOR2	ENST00000613507.4	TSL:5	c.-26-23523G>T		intron	N/A	ENSP00000482957.1	Q9Y4F9-1

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70392 AN: 151846 Hom.: 17323 Cov.: 32

Gnomad AFR AF: 0.626

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.508

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.415

Gnomad OTH AF: 0.443

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

GnomAD4 genome AF: 0.464 AC: 70452 AN: 151964 Hom.: 17344 Cov.: 32 AF XY: 0.457 AC XY: 33916 AN XY: 74256

African (AFR) AF: 0.626 AC: 25931 AN: 41440

American (AMR) AF: 0.425 AC: 6486 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 989 AN: 3464

East Asian (EAS) AF: 0.280 AC: 1449 AN: 5178

South Asian (SAS) AF: 0.508 AC: 2451 AN: 4822

European-Finnish (FIN) AF: 0.332 AC: 3496 AN: 10524

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.415 AC: 28194 AN: 67952

Other (OTH) AF: 0.440 AC: 929 AN: 2112

Alfa AF: 0.495 Hom.: 7495

Bravo AF: 0.470

Asia WGS AF: 0.411 AC: 1429 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	13
DANN	Benign	0.74
PhyloP100		0.39
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2817723; hg19: chr6-24899568;