rs2207401

Positions:

• chr6-24882753-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.68).
• 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/exons	MANE	Protein	UniProt
RIPOR2	NM_001286445.3	c.62-6936G>A		intron_variant		ENST00000643898.2	NP_001273374.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIPOR2	ENST00000643898.2	c.62-6936G>A		intron_variant			NM_001286445.3	ENSP00000494268	A2

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

Gnomad4 AFR AF: 0.201

Gnomad4 AMR AF: 0.0726

Gnomad4 ASJ AF: 0.0833

Gnomad4 EAS AF: 0.0204

Gnomad4 SAS AF: 0.104

Gnomad4 FIN AF: 0.0334

Gnomad4 NFE AF: 0.0668

Gnomad4 OTH AF: 0.113

Alfa AF: 0.0780 Hom.: 229

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

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: rs2207401; hg19: chr6-24882981;