rs2817723

chr6-24899340-C-Achr6-24899340-C-G

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RIPOR2	NM_001286445.3	c.62-23523G>T		intron_variant		ENST00000643898.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIPOR2	ENST00000643898.2	c.62-23523G>T		intron_variant			NM_001286445.3	A2

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

Gnomad4 AFR AF: 0.626

Gnomad4 AMR AF: 0.425

Gnomad4 ASJ AF: 0.286

Gnomad4 EAS AF: 0.280

Gnomad4 SAS AF: 0.508

Gnomad4 FIN AF: 0.332

Gnomad4 NFE AF: 0.415

Gnomad4 OTH AF: 0.440

Alfa AF: 0.442 Hom.: 1953

Bravo AF: 0.470

Asia WGS AF: 0.411 AC: 1429 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
Cadd	Benign	13
Dann	Benign	0.74

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

Publications

LitVar

Other links and lift over

dbSNP: rs2817723; hg19: chr6-24899568;