chr2-205113577-G-GGTA
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_ModeratePM2
The ENST00000406610.7(PARD3B):c.680_680+1insGTA variant causes a splice donor, intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000622 in 1,607,334 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )
Consequence
PARD3B
ENST00000406610.7 splice_donor, intron
ENST00000406610.7 splice_donor, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 8.71
Genes affected
PARD3B (HGNC:14446): (par-3 family cell polarity regulator beta) Predicted to enable phosphatidylinositol binding activity. Predicted to be involved in several processes, including establishment of cell polarity; establishment of centrosome localization; and establishment or maintenance of epithelial cell apical/basal polarity. Located in cell junction. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PVS1
Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.024046434 fraction of the gene. Cryptic splice site detected, with MaxEntScore 5.7, offset of 0 (no position change), new splice context is: aagGTagta. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in inframe change.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 151978Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000413 AC: 1AN: 242050Hom.: 0 AF XY: 0.00000760 AC XY: 1AN XY: 131584
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GnomAD4 exome AF: 0.00000481 AC: 7AN: 1455356Hom.: 0 Cov.: 30 AF XY: 0.00000552 AC XY: 4AN XY: 724160
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 151978Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74224
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
PARD3B-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 27, 2023 | The PARD3B c.680+1_680+3dupGTA variant is predicted to result in an intronic duplication. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.00090% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/2-205978301-G-GGTA). Other variants predicted to impact splicing have been reported in association with neurodevelopmental phenotypes (Stessman et al. 2017. PubMed ID: 28191889). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
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Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at