rs576572225
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PP3
The NM_057093.2(CRYBA2):c.286C>T(p.Arg96Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000812 in 1,613,222 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_057093.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CRYBA2 | NM_057093.2 | c.286C>T | p.Arg96Trp | missense_variant | Exon 2 of 4 | ENST00000295728.7 | NP_476434.1 | |
CRYBA2 | NM_057094.2 | c.286C>T | p.Arg96Trp | missense_variant | Exon 3 of 5 | NP_476435.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CRYBA2 | ENST00000295728.7 | c.286C>T | p.Arg96Trp | missense_variant | Exon 2 of 4 | 1 | NM_057093.2 | ENSP00000295728.2 | ||
CRYBA2 | ENST00000392096.6 | c.286C>T | p.Arg96Trp | missense_variant | Exon 3 of 5 | 1 | ENSP00000375946.2 | |||
CRYBA2 | ENST00000453769.1 | c.286C>T | p.Arg96Trp | missense_variant | Exon 3 of 4 | 3 | ENSP00000395120.1 | |||
CRYBA2 | ENST00000490678.1 | n.288C>T | non_coding_transcript_exon_variant | Exon 2 of 2 | 2 |
Frequencies
GnomAD3 genomes AF: 0.000112 AC: 17AN: 152262Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.0000930 AC: 23AN: 247402Hom.: 0 AF XY: 0.000119 AC XY: 16AN XY: 134162
GnomAD4 exome AF: 0.0000780 AC: 114AN: 1460842Hom.: 0 Cov.: 31 AF XY: 0.0000977 AC XY: 71AN XY: 726692
GnomAD4 genome AF: 0.000112 AC: 17AN: 152380Hom.: 1 Cov.: 32 AF XY: 0.000134 AC XY: 10AN XY: 74528
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.286C>T (p.R96W) alteration is located in exon 2 (coding exon 2) of the CRYBA2 gene. This alteration results from a C to T substitution at nucleotide position 286, causing the arginine (R) at amino acid position 96 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not provided Uncertain:1
The CRYBA2 p.Arg96Trp variant was not identified in the literature nor was it identified in ClinVar. The variant was identified in dbSNP (ID: rs576572225). The variant was identified in control databases in 25 of 278808 chromosomes at a frequency of 0.00008967 (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: South Asian in 13 of 30508 chromosomes (freq: 0.000426), African in 2 of 24836 chromosomes (freq: 0.000081), European (non-Finnish) in 9 of 125756 chromosomes (freq: 0.000072), Latino in 1 of 35312 chromosomes (freq: 0.000028), but was not observed in the Ashkenazi Jewish, East Asian, European (Finnish), or Other populations. The p.Arg96 residue is conserved across mammals and other organisms, and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) suggest that the variant may impact the protein; however, this information is not predictive enough to assume pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at