22-20086006-G-A
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PP2BP4_StrongBP6BS2
The NM_022720.7(DGCR8):c.43G>A(p.Ala15Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000106 in 1,610,296 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_022720.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DGCR8 | NM_022720.7 | c.43G>A | p.Ala15Thr | missense_variant | 2/14 | ENST00000351989.8 | |
DGCR8 | NM_001190326.2 | c.43G>A | p.Ala15Thr | missense_variant | 2/13 | ||
DGCR8 | XM_047441418.1 | c.43G>A | p.Ala15Thr | missense_variant | 2/14 | ||
DGCR8 | XM_047441419.1 | c.43G>A | p.Ala15Thr | missense_variant | 2/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DGCR8 | ENST00000351989.8 | c.43G>A | p.Ala15Thr | missense_variant | 2/14 | 1 | NM_022720.7 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000335 AC: 51AN: 152222Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000112 AC: 28AN: 249126Hom.: 1 AF XY: 0.0000668 AC XY: 9AN XY: 134814
GnomAD4 exome AF: 0.0000823 AC: 120AN: 1457956Hom.: 0 Cov.: 32 AF XY: 0.0000759 AC XY: 55AN XY: 724788
GnomAD4 genome AF: 0.000335 AC: 51AN: 152340Hom.: 0 Cov.: 32 AF XY: 0.000282 AC XY: 21AN XY: 74496
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 08, 2023 | The c.43G>A (p.A15T) alteration is located in exon 2 (coding exon 1) of the DGCR8 gene. This alteration results from a G to A substitution at nucleotide position 43, causing the alanine (A) at amino acid position 15 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
DGCR8-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 02, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at