11-110264881-CACA-C

Position:

• chr11-110264881-CACA-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_002906.4(RDX):​c.97-10_97-8del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000513 in 1,611,124 control chromosomes in the GnomAD database, including 11 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00057 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00051 (11 hom.)
• Consequence: RDX NM_002906.4 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.33

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 11-110264881-CACA-C is Benign according to our data. Variant chr11-110264881-CACA-C is described in ClinVar as [Likely_benign]. Clinvar id is 179830.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000572 (87/152146) while in subpopulation SAS AF= 0.00374 (18/4814). AF 95% confidence interval is 0.00242. There are 0 homozygotes in gnomad4. There are 56 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RDX	NM_002906.4	c.97-10_97-8del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000645495.2	NP_002897.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RDX	ENST00000645495.2	c.97-10_97-8del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NM_002906.4	ENSP00000496503	P1

Frequencies

GnomAD3 genomes AF: 0.000566 AC: 86 AN: 152028 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000893

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.00374

Gnomad FIN AF: 0.000663

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.000957

GnomAD3 exomes AF: 0.000857 AC: 215 AN: 250794 Hom.: 1 AF XY: 0.000981 AC XY: 133 AN XY: 135572

Gnomad AFR exome AF: 0.000924

Gnomad AMR exome AF: 0.000318

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000218

Gnomad SAS exome AF: 0.00416

Gnomad FIN exome AF: 0.00140

Gnomad NFE exome AF: 0.000238

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000507 AC: 740 AN: 1458978 Hom.: 11 AF XY: 0.000625 AC XY: 454 AN XY: 726002

Gnomad4 AFR exome AF: 0.00141

Gnomad4 AMR exome AF: 0.000291

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.000151

Gnomad4 SAS exome AF: 0.00420

Gnomad4 FIN exome AF: 0.00160

Gnomad4 NFE exome AF: 0.000153

Gnomad4 OTH exome AF: 0.000414

GnomAD4 genome AF: 0.000572 AC: 87 AN: 152146 Hom.: 0 Cov.: 32 AF XY: 0.000753 AC XY: 56 AN XY: 74400

Gnomad4 AFR AF: 0.000915

Gnomad4 AMR AF: 0.000262

Gnomad4 ASJ AF: 0.000577

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.00374

Gnomad4 FIN AF: 0.000663

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.000947

Bravo AF: 0.000438

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 20, 2022	See Variant Classification Assertion Criteria. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Oct 03, 2023	- -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Jun 23, 2016

c.97-19TGT[3] in intron 3 of RDX: This variant is not expected to have clinical significance because it has been identified in 0.35% (57/16200) of South Asian c hromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute .org). -

RDX-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 21, 2020

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

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: rs532650829; hg19: chr11-110135606;