rs879255251
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_173689.7(CRB2):c.3089_3104delGGCCCGGCGCGGCCCC(p.Arg1030LeufsTer106) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000386 in 1,374,404 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_173689.7 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CRB2 | ENST00000373631.8 | c.3089_3104delGGCCCGGCGCGGCCCC | p.Arg1030LeufsTer106 | frameshift_variant | Exon 10 of 13 | 1 | NM_173689.7 | ENSP00000362734.3 | ||
CRB2 | ENST00000359999.7 | c.3089_3104delGGCCCGGCGCGGCCCC | p.Arg1030LeufsTer138 | frameshift_variant | Exon 10 of 10 | 2 | ENSP00000353092.3 | |||
CRB2 | ENST00000460253.1 | n.2093_2108delGGCCCGGCGCGGCCCC | non_coding_transcript_exon_variant | Exon 5 of 9 | 2 | ENSP00000435279.1 |
Frequencies
GnomAD3 genomes AF: 0.0000528 AC: 8AN: 151596Hom.: 0 Cov.: 34
GnomAD4 exome AF: 0.0000368 AC: 45AN: 1222808Hom.: 0 AF XY: 0.0000434 AC XY: 26AN XY: 598848
GnomAD4 genome AF: 0.0000528 AC: 8AN: 151596Hom.: 0 Cov.: 34 AF XY: 0.0000405 AC XY: 3AN XY: 74058
ClinVar
Submissions by phenotype
CRB2-related disorder Pathogenic:1
The CRB2 c.3089_3104del16 variant is predicted to result in a frameshift and premature protein termination (p.Arg1030Leufs*106). This variant has been reported in the compound heterozygous state in a fetus with ventriculomegaly, hydrocephalus, and echogenic kidneys (Zhang et al. 2020. PubMed ID: 32051522). This variant is reported in 1 of 59,000 alleles in gnomAD: However, the quality of this call is questionable and should be interpreted with caution (http://gnomad.broadinstitute.org/variant/9-126135887-TGGCGCGGCCCCGGCCC-T). Frameshift variants in CRB2 are expected to be pathogenic. This variant is interpreted as likely pathogenic. -
not provided Pathogenic:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at