rs2298501

Variant names:

• chr11-110195809-G-A
• rs2298501
• ENST00000528900.5:c.*388C>T

Variant summary

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

The ENST00000528900.5(RDX):​c.*388C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 151,962 control chromosomes in the GnomAD database, including 11,648 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 0.39 (11648 hom., cov: 32)
  • Exomes 𝑓: 0.083 (0 hom.)
• Consequence: RDX ENST00000528900.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.489
• Publications: 2 publications found

Genes affected

RDX (HGNC:9944): (radixin) Radixin is a cytoskeletal protein that may be important in linking actin to the plasma membrane. It is highly similar in sequence to both ezrin and moesin. The radixin gene has been localized by fluorescence in situ hybridization to 11q23. A truncated version representing a pseudogene (RDXP2) was assigned to Xp21.3. Another pseudogene that seemed to lack introns (RDXP1) was mapped to 11p by Southern and PCR analyses. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2012]

RDX Gene-Disease associations (from GenCC):

• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• autosomal recessive nonsyndromic hearing loss 24

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RDX	NM_001260492.2	c.*388C>T		3_prime_UTR_variant	Exon 16 of 16		NP_001247421.1
RDX	NM_001440511.1	c.*388C>T		3_prime_UTR_variant	Exon 15 of 15		NP_001427440.1
RDX	NM_001260495.2	c.*388C>T		3_prime_UTR_variant	Exon 9 of 9		NP_001247424.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RDX	ENST00000528900.5	c.*388C>T		3_prime_UTR_variant	Exon 9 of 9	1		ENSP00000433580.1
RDX	ENST00000530301.5	c.*388C>T		3_prime_UTR_variant	Exon 8 of 8	1		ENSP00000436277.1
RDX	ENST00000528498.5	c.*31+3772C>T		intron_variant	Intron 15 of 15	1		ENSP00000432112.1

Frequencies

GnomAD3 genomes AF: 0.388 AC: 58846 AN: 151830 Hom.: 11642 Cov.: 32

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.603

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.446

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.362

GnomAD4 exome AF: 0.0833 AC: 1 AN: 12 Hom.: 0 Cov.: 0 AF XY: 0.125 AC XY: 1 AN XY: 8

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.100 AC: 1 AN: 10

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.388 AC: 58892 AN: 151950 Hom.: 11648 Cov.: 32 AF XY: 0.388 AC XY: 28833 AN XY: 74262

African (AFR) AF: 0.324 AC: 13406 AN: 41422

American (AMR) AF: 0.364 AC: 5563 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1200 AN: 3470

East Asian (EAS) AF: 0.602 AC: 3115 AN: 5176

South Asian (SAS) AF: 0.399 AC: 1922 AN: 4820

European-Finnish (FIN) AF: 0.446 AC: 4696 AN: 10526

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.407 AC: 27690 AN: 67960

Other (OTH) AF: 0.365 AC: 769 AN: 2104

Alfa AF: 0.394 Hom.: 1483

Bravo AF: 0.379

Asia WGS AF: 0.468 AC: 1631 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	8.4
DANN	Benign	0.67
PhyloP100		-0.49
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2298501; hg19: chr11-110066534;