22-19039046-C-T
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_005137.3(DGCR2):c.1472G>A(p.Arg491Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00011 in 1,612,962 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R491P) has been classified as Uncertain significance.
Frequency
Consequence
NM_005137.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DGCR2 | NM_005137.3 | c.1472G>A | p.Arg491Gln | missense_variant | 10/10 | ENST00000263196.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DGCR2 | ENST00000263196.12 | c.1472G>A | p.Arg491Gln | missense_variant | 10/10 | 1 | NM_005137.3 | P1 | |
DGCR2 | ENST00000389262.8 | c.*1043G>A | 3_prime_UTR_variant, NMD_transcript_variant | 11/11 | 1 | ||||
DGCR2 | ENST00000537045.5 | c.1349G>A | p.Arg450Gln | missense_variant | 9/9 | 2 | |||
DGCR2 | ENST00000467659.1 | n.1250G>A | non_coding_transcript_exon_variant | 4/4 | 5 |
Frequencies
GnomAD3 genomes AF: 0.000131 AC: 20AN: 152214Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.000190 AC: 47AN: 247466Hom.: 0 AF XY: 0.000223 AC XY: 30AN XY: 134430
GnomAD4 exome AF: 0.000108 AC: 158AN: 1460748Hom.: 1 Cov.: 30 AF XY: 0.000105 AC XY: 76AN XY: 726682
GnomAD4 genome AF: 0.000131 AC: 20AN: 152214Hom.: 0 Cov.: 34 AF XY: 0.000161 AC XY: 12AN XY: 74356
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 28, 2023 | The c.1472G>A (p.R491Q) alteration is located in exon 10 (coding exon 10) of the DGCR2 gene. This alteration results from a G to A substitution at nucleotide position 1472, causing the arginine (R) at amino acid position 491 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at