rs886044841
Variant summary
Our verdict is Pathogenic. Variant got 20 ACMG points: 20P and 0B. PVS1PP3_StrongPP5_Very_Strong
The NM_001256789.3(CACNA1F):c.2543+1G>A variant causes a splice donor change. The variant allele was found at a frequency of 0.00000275 in 1,088,971 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (★★).
Frequency
Consequence
NM_001256789.3 splice_donor
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNA1F | NM_001256789.3 | c.2543+1G>A | splice_donor_variant | ENST00000323022.10 | |||
CACNA1F | NM_001256790.3 | c.2381+1G>A | splice_donor_variant | ||||
CACNA1F | NM_005183.4 | c.2576+1G>A | splice_donor_variant | ||||
CACNA1F | XM_011543983.3 | c.2381+1G>A | splice_donor_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA1F | ENST00000323022.10 | c.2543+1G>A | splice_donor_variant | 1 | NM_001256789.3 | ||||
CACNA1F | ENST00000376251.5 | c.2381+1G>A | splice_donor_variant | 1 | |||||
CACNA1F | ENST00000376265.2 | c.2576+1G>A | splice_donor_variant | 1 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 22
GnomAD3 exomes AF: 0.00000614 AC: 1AN: 162946Hom.: 0 AF XY: 0.0000193 AC XY: 1AN XY: 51690
GnomAD4 exome AF: 0.00000275 AC: 3AN: 1088971Hom.: 0 Cov.: 33 AF XY: 0.00000561 AC XY: 2AN XY: 356359
GnomAD4 genome ? Cov.: 22
ClinVar
Submissions by phenotype
not provided Pathogenic:3
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Nov 04, 2023 | This sequence change affects a donor splice site in intron 20 of the CACNA1F gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CACNA1F are known to be pathogenic (PMID: 9662399, 11281458, 17525176, 22194652, 24124559, 26992781). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with congenital stationary night blindness (PMID: 22183355, 28838317, 30825406). ClinVar contains an entry for this variant (Variation ID: 285396). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. - |
Pathogenic, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 25, 2016 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Mar 25, 2024 | Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 28838317, 30825406, 22183355, 33668843) - |
CACNA1F-related disorder Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 27, 2024 | The CACNA1F c.2576+1G>A variant is predicted to disrupt the GT donor site and interfere with normal splicing. This variant has been reported in multiple patients/families with X-linked congenital stationary night blindness (CSNB) incomplete type 2A (Wang et al. 2017. PubMed ID: 28838317; Zeitz et al. 2019. PubMed ID: 30825406; Lodha et al. 2012. PubMed ID: 22183355). This variant is reported in 0.0014% of alleles in individuals of European (non-Finnish) descent in gnomAD. Variants that disrupt the consensus splice donor site in CACNA1F are expected to be pathogenic. This variant is interpreted as pathogenic. - |
Ocular albinism, type II;C1845407:X-linked cone-rod dystrophy 3;C1848172:Congenital stationary night blindness 2A Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Sep 10, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at