rs532650829

Variant names:

• chr11-110264881-CACA-C
• rs532650829
• NM_002906.4:c.97-10_97-8delTGT

Your query was ambiguous. Multiple possible variants found:

• chr11-110264881-CACA-C
• chr11-110264881-CACA-CACAACA

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_002906.4(RDX):​c.97-10_97-8delTGT variant causes a splice region, 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, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 1.33
• 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), Ambry Genetics
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 11 AR gene

Variant Effect in Transcripts

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

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RDX	NM_002906.4	MANE Select	c.97-10_97-8delTGT		splice_region intron	N/A	NP_002897.1	B0YJ88
	RDX	NM_001440509.1		c.97-10_97-8delTGT		splice_region intron	N/A	NP_001427438.1
	RDX	NM_001260492.2		c.97-10_97-8delTGT		splice_region intron	N/A	NP_001247421.1	P35241-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RDX	ENST00000645495.2	MANE Select	c.97-10_97-8delTGT		splice_region intron	N/A	ENSP00000496503.2	P35241-1
	RDX	ENST00000528498.5	TSL:1	c.97-10_97-8delTGT		splice_region intron	N/A	ENSP00000432112.1	P35241-5
	RDX	ENST00000528900.5	TSL:1	c.-83+14797_-83+14799delTGT		intron	N/A	ENSP00000433580.1	P35241-2

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

GnomAD2 exomes AF: 0.000857 AC: 215 AN: 250794 AF XY: 0.000981

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 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

African (AFR) AF: 0.00141 AC: 47 AN: 33420

American (AMR) AF: 0.000291 AC: 13 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26110

East Asian (EAS) AF: 0.000151 AC: 6 AN: 39650

South Asian (SAS) AF: 0.00420 AC: 362 AN: 86166

European-Finnish (FIN) AF: 0.00160 AC: 85 AN: 53162

Middle Eastern (MID) AF: 0.00539 AC: 31 AN: 5756

European-Non Finnish (NFE) AF: 0.000153 AC: 170 AN: 1109684

Other (OTH) AF: 0.000414 AC: 25 AN: 60320

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

African (AFR) AF: 0.000915 AC: 38 AN: 41536

American (AMR) AF: 0.000262 AC: 4 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 2 AN: 3464

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5178

South Asian (SAS) AF: 0.00374 AC: 18 AN: 4814

European-Finnish (FIN) AF: 0.000663 AC: 7 AN: 10556

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 67996

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000438

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000593

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)
-	-	1	RDX-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs532650829; hg19: chr11-110135606;