19-3770753-CCCCGGG-CCCCGGGCCCGGG
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM4BS1_SupportingBS2
The NM_001319074.4(RAX2):c.417_422dupCCCGGG(p.Gly141_Leu142insProGly) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00032 in 1,531,106 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001319074.4 disruptive_inframe_insertion
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RAX2 | NM_001319074.4 | c.417_422dupCCCGGG | p.Gly141_Leu142insProGly | disruptive_inframe_insertion | Exon 3 of 3 | ENST00000555633.3 | NP_001306003.2 | |
RAX2 | NM_032753.4 | c.417_422dupCCCGGG | p.Gly141_Leu142insProGly | disruptive_inframe_insertion | Exon 3 of 3 | NP_116142.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RAX2 | ENST00000555633.3 | c.417_422dupCCCGGG | p.Gly141_Leu142insProGly | disruptive_inframe_insertion | Exon 3 of 3 | 1 | NM_001319074.4 | ENSP00000450456.3 | ||
RAX2 | ENST00000555978.5 | c.417_422dupCCCGGG | p.Gly141_Leu142insProGly | disruptive_inframe_insertion | Exon 3 of 3 | 1 | ENSP00000450687.2 |
Frequencies
GnomAD3 genomes AF: 0.000145 AC: 22AN: 152196Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000733 AC: 92AN: 125538Hom.: 0 AF XY: 0.000929 AC XY: 64AN XY: 68876
GnomAD4 exome AF: 0.000339 AC: 468AN: 1378794Hom.: 4 Cov.: 31 AF XY: 0.000444 AC XY: 302AN XY: 680382
GnomAD4 genome AF: 0.000144 AC: 22AN: 152312Hom.: 0 Cov.: 33 AF XY: 0.000175 AC XY: 13AN XY: 74472
ClinVar
Submissions by phenotype
Cone-rod dystrophy 11 Pathogenic:2
- -
This variant (reported as, 140P_141Gdup) was previously reported in a patient with cone-rod dystrophy in heterozygous state and also identified in the proband's mother and two siblings with normal vision but possibility of mild CORD could not be excluded in them as mentioned in the article. Functional studies using co-immunoprecipitation analysis suggested proteins with the variant have decreased interaction with Crx and increased transactivation activity [PMID: 15028672]. -
not provided Benign:1
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at