NM_001286445.3:c.61+16951T>C

Variant names:

• chr6-24918887-A-G
• rs2064524
• NM_001286445.3:c.61+16951T>C

Variant summary

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

The NM_001286445.3(RIPOR2):​c.61+16951T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 151,984 control chromosomes in the GnomAD database, including 23,181 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 0.52 (23181 hom., cov: 32)
• Consequence: RIPOR2 NM_001286445.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0940
• Publications: 6 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.807 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIPOR2	NM_001286445.3	c.61+16951T>C		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.61+16951T>C		intron_variant	Intron 1 of 21		NM_001286445.3	ENSP00000494268.2

Frequencies

GnomAD3 genomes AF: 0.517 AC: 78499 AN: 151866 Hom.: 23147 Cov.: 32

Gnomad AFR AF: 0.814

Gnomad AMI AF: 0.481

Gnomad AMR AF: 0.456

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.478

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.499

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

GnomAD4 genome AF: 0.517 AC: 78579 AN: 151984 Hom.: 23181 Cov.: 32 AF XY: 0.508 AC XY: 37767 AN XY: 74280

African (AFR) AF: 0.814 AC: 33756 AN: 41460

American (AMR) AF: 0.455 AC: 6943 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 997 AN: 3466

East Asian (EAS) AF: 0.281 AC: 1453 AN: 5176

South Asian (SAS) AF: 0.477 AC: 2296 AN: 4818

European-Finnish (FIN) AF: 0.331 AC: 3495 AN: 10544

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.412 AC: 28028 AN: 67962

Other (OTH) AF: 0.495 AC: 1041 AN: 2104

Alfa AF: 0.416 Hom.: 7500

Bravo AF: 0.535

Asia WGS AF: 0.424 AC: 1473 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.0
DANN	Benign	0.81
PhyloP100		-0.094
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: rs2064524; hg19: chr6-24919115;