chr11-110237662-A-G

Variant names:

• chr11-110237662-A-G
• rs876657572
• NM_002906.4:c.1091-10T>C

GermlineCancer (beta)

Variant summary

Our verdict is Uncertain significance.

+2 Uncertain · Warm

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received 2 classification points (ACGS-UK Somatic Oncogenicity v2025). O3_Moderate

The NM_002906.4(RDX):c.1091-10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The gene RDX is a tumor suppressor gene (CancerMine: 2 TSG citations). The variant allele was found at a cumulative frequency of 0.00000137 (AC=2) in the gnomAD database across 1,461,300 control chromosomes (no homozygotes observed). The grpmax filtering allele frequency (95% CI) is 0.0000003. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Variant has been reported in ClinVar as Benign/Likely Benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RDX NM_002906.4 intron
• Scores: Splicing: ADA: 0.003096
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.29
• Publications: 0 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: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Classification according to ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript:

Our verdict: Uncertain_significance. The variant received 2 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	O3Absent or very rare in population		Absent or extremely rare in gnomAD (AC ≤ 2) — O3 moderate; GnomAD: AF = 0.000000, AC = 2 — absent/extremely rare (O3 moderate [+2])

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_002906.4. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	RDX NM_002906.4	MANE Select	c.1091-10T>C	intron	Intron 10 of 13	Prot: NP_002897.1 UniProt:
	RDX NM_001440509.1		c.1277-10T>C	intron	Intron 11 of 14	Prot: NP_001427438.1
	RDX NM_001260492.2		c.1091-10T>C	intron	Intron 10 of 15	Prot: NP_001247421.1 UniProt:

RDX NM_002906.4

MANE Select

HGVSc / HGVSpc.1091-10T>C

Exon rankIntron 10 of 13

intron

Prot: NP_002897.1UniProt: B0YJ88P35241-1

RDX NM_001440509.1

HGVSc / HGVSpc.1277-10T>C

Exon rankIntron 11 of 14

intron

Prot: NP_001427438.1

RDX NM_001260492.2

HGVSc / HGVSpc.1091-10T>C

Exon rankIntron 10 of 15

intron

Prot: NP_001247421.1UniProt: P35241-5

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	RDX ENST00000645495.2	MANE Select	c.1091-10T>C	intron	Intron 10 of 13	Prot: ENSP00000496503.2 UniProt:
	RDX ENST00000528498.5	TSL:1	c.1091-10T>C	intron	Intron 10 of 15	Prot: ENSP00000432112.1 UniProt:
	RDX ENST00000528900.5	TSL:1	c.50-10T>C	intron	Intron 3 of 8	Prot: ENSP00000433580.1 UniProt:

RDX ENST00000645495.2

MANE Select

HGVSc / HGVSpc.1091-10T>C

Exon rankIntron 10 of 13

intron

Prot: ENSP00000496503.2UniProt: P35241-1

RDX ENST00000528498.5

TSL:1

HGVSc / HGVSpc.1091-10T>C

Exon rankIntron 10 of 15

intron

Prot: ENSP00000432112.1UniProt: P35241-5

RDX ENST00000528900.5

TSL:1

HGVSc / HGVSpc.50-10T>C

Exon rankIntron 3 of 8

intron

Prot: ENSP00000433580.1UniProt: P35241-2

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 3 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:32
GnomAD4 exome	AF: 0.00000137	AC:2	Hom:0	AN:1461300	Cov:30
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:32

Showing 3 sources

Case/control cohorts

Cohort	Cases			Controls
	AF	AC	AN	AF	AC	AN
BipEx(Bipolar disorder (including schizoaffective))	0.0000352	1	28420	0.00	0	28844

Showing 1 cohortAllele count / allele number. AF is computed from the counts for ASC (not provided by the source).

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	8.8
BayesDel_noAF	Benign	-0.75
BranchPoint Hunter	N/A	4.0
CADD	Benign	1.5
DANN	Benign	0.59
GPN-Star LLR	N/A	-2.5
GPN-Star score	N/A	2.5
PhyloP100	Benign	3.3

Showing 8 of 8 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
dbscSNV1_ADA	Benign	0.0031
dbscSNV1_RF	Benign	0.080
DS_AL_spliceai	Uncertain	0.22	Position offset: -10
Pangolin (max)	Benign	0.090
SpliceAI score (max)	Uncertain	0.22	Details are displayed if max score is > 0.2

Showing 5 of 5 scores

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs876657572;

hg19: chr11-110108387;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar